tobacco and health

2
TABLE OF CONTENTS
S.NO. TITLE PAGE NO
1. INTRODUCTION 13
2. HISTORY OF TOBACCO 14
I. Global history of tobacco
14
II. Indian history of tobacco
18
3. TYPES OF TOBACCO 20
I. Botanical types of tobacco
20
II. Commercial types of tobacco
21
4.
TOBACCO CULTIVATION AND PROCESSING
30
I. Cultivation of tobacco
31
II. Processing of tobacco
34
5. COMPONENTS AND PHARMACOLOGY OF TOBACCO 38
I. Components of tobacco
38
II. Pharmacology of tobacco
39
6. IMPACT OF TOBACCO 41
I. Impact of tobacco on economy
41
II. Social and environmental consequences
44

3
7. IMPACT OF TOBACCO IN HEALTH 47
I. Traditional uses of tobacco
47
II. Detrimental effects on tobacco
51
8. TOBACCO CONTROL MEASURES 90
I. Global tobacco control measures 91
II. National tobacco control measures in India 101
9 CONCLUSION 99

4
APPENDIX 1
LIST OF TABLES
S.NO. LEGENDS
1.
Smoking tobacco - Flue-cured tobacco
2.
Smoking Tobacco – Bidi
3.
Chewing Tobacco
4. Miscellaneous varieties of tobacco
5.
Carcinogens in tobacco smoke
6.
Carcinogens in certain type of cancer
7. Carcinogenic compounds in Smokeless Tobacco

5
APPENDIX 2
LIST OF FIGURES
S.NO. LEGENDS
1. Tobacco warehouse
2. Night riders
3.
Quotes of warning from the Night riders
4. N. Tabacum
5. Roll-Your-Own (RYO) cigarette
6. Women smoking large cigar
7. Women smoking Cheroot
8.
Kretek
9.
Pipe smoking
10.
Water pipe
11.
Betel quid
12.
Paan
13.
Gutkha
14.
Man ingesting Gutkha
15.
Gudakhu
16.
Khaini

6
17.
Khaini mixed with slaked lime
18.
Moist and Dry snuff, Snus
19.
Tobacco cultivation
20.
Steps in cultivation of tobacco plant
21.
Air curing
22.
Fire curing
23.
Flue curing
24.
Sun curing
25.
Curing methods of tobacco
26.
Steps in processing of tobacco
27.
Overview of GTSS
28.
MPOWER
29.
The 5A’s
30.
The 5R’s
31.
Benefits of quitting smoking
32.
The Pictorial warnings for smoking and smokeless
tobacco
33.
The Pictorial warnings for smoking and smokeless
tobacco
34.
GATS India

7
35.
No smoking logos in public places

8
APPENDIX 3
ABBREVIATIONS
WHO World Health Organization
ICAR
Indian Council of Agricultural Research
RYO Roll-Your-Own
SLT
Smokeless tobacco
FCV Flue Cured Virginia
CTRI Central tobacco research institute
TS
Tobacco Smoke
PAH Polycyclic Aromatic Hydrocarbons
NNK
4 (Methylnitrosamino)-1-(3-pyridyl)-1-butanone
NNN
N-nitrosonornicotine
VC
Vinyl Chloride
GSTs
Glutathione-S-Transferases
UGTs
Uridine-5′-Diphosphate-Glucuronosyltransferases
NATs
N-acetyl-transferases
ETS
Environmental Tobacco Smoke
COPD
Chronic Obstructive Pulmonary Disease
TB
Tuberculosis

9
CVD Cardiovascular Diseases
CO
Carbon monoxide
Cd
Cadmium
CHD
Coronary Heart Disease
OPMD Oral Potentially Malignant Disorders
OSCC Oral Squamous Cell Carcinoma
OSMF Oral submucous Fibrosis
FCTC Framework Convention on Tobacco Control
TobReg Tobacco Product Regulation
TFI Tobacco Free Initiative
GTSS Global Tobacco Surveillance System
GYTS Global Youth Tobacco Survey
GATS Global Adult Tobacco Survey
SHS Second Hand Smoking

10
INTRODUCTION
The herb, Tobacco holds a long history by facing both the extreme ends of
gloriousness and dreadfulness.Tobacco is the common term, for many plants from Nicotiana
genus, nightshade family. The plant is indigenous to America, and now it is cultivated across
the world. Records states that Christopher Columbus, an Italian, contributed to the spread of
the tobacco plant worldwide. There are 70 species of Nicotiana genus recognised, and about
45 of them can be found in India.
In the olden days it was considered as a God sent remedy for all diseases. It was used
either alone or with mixture of different native herbs, to cure almost all ailments of the
human body, and also for animals. Thus tobacco behaved as a medicine and as a tradition in
the lives of ancient people.As time went by the people started to know its addictive properties
and used it in abusive ways. Both the smoking and smokeless tobacco products have equal
negative effects over the health of humans. Tobacco production has a huge impact in
economy, health and environmental factors.
Papers and books were published about the health warnings of the tobacco products.
But the process of production and consumption of these products continued among the people
from then till now. The WHO and other organisations started to make policies and program to
increase awareness among the people about the ill effects of these products. In all times, there
exists confusion regarding the tobacco as a boon or a curse among the society.
The literature available from these search engines: NCBI Bookshelf, Text books,
books from PDF drive, articles index in Pubmed and a few blogs were used in this book
compilation. In this review, briefing on the history of tobacco, its types, manufacturing, the
impact of tobacco on economy, social and environment consequences with major discussion
on the impact of tobacco in health is done.

11
HISTORY OF TOBACCO
I. GLOBAL HISTORY OF TOBACCO:
6000 B.C, 1 B.C
It is believed that Native Americans cultivated tobacco since 6000 B.C and by 1 B.C,
the usage of tobacco skyrocketed among them. The cultivated tobacco was of two species-
one was “Nicotiana rustica” and the other was “Nicotiana tabacum” which were dispersed in
Southern and Northern parts of America, especially in the regions of Andes.(1, 2, 3)
This
indicated the native origin of tobacco, which was also backed by various archaeological,
botanical, anthropological and antiquity records.(1,2)
1400s
The written documentation of tobacco began in the year 1492 by Christopher
Columbus, an Italian who discovered the sailing route to America. He developed the interest
on observing Native Americans smoking habits and the way of treating illness with a herb
which he had never seen before. He decided to take those herbs to Europe, thereby initiated
the spread of tobacco worldwide. At the same time, tobacco cultivation started in Cuba
followed by Middle East. (1,4)
1500s
The Chinese cultivated their first plantation of tobacco in 1530. In 1531, the
cultivation took place in Santo Domingo (America) which was initiated by the European
settlers.(4)
The word Tobacco underwent a variety of pronunciation and spelling changes until
when John Florio published an Italian – English Dictionary “World of Words” in London in
1598 mentioning tobacco as “Nicosiana” (Italian). Nicosiana in English means “The herb
Tobacco”. During this period tobacco got its attention worldwide. It didn’t leave Indian soil
as well.(2)
1600s

12
From the beginning of 16th century till the end of 19th
century, this plant enjoyed a
widespread reach especially for its medicinal values whose beneficial uses were stated as
almost endless. (1)
In 1600s, Tobacco was introduced by Portuguese in India, and had a huge impact in
India. By 1603, tobacco cultivation was well established in Japan and in 1604, in England,
King James I wrote a paper ‘A Counterblaste to Tobacco’ where he highlights the ill effects
of tobacco. In1612, America started to grow tobacco for commercial purposes whereas in
1633, Turkey announced death penalty for smoking.At the same time a Chinese philosopher
named Fang Yinhi said that continuous smoking of tobacco for a long period of time shall
‘scorche one’s lungs’. By the end of 16th
century tobacco usage became a custom among the
people of Europe and they also exported it to India, China and Japan.(1,4)
1700s
In England, in the year 1761, the first study was made on the effects of tobacco
among snuff users by John Hill and he stated that snuff users had risk of developing nasal
cancers. In 1795, Samuel Thomas Von Soemmering from Germany reported the development
of cancer of lip in the pipe smokers.(4)
1800s
In 1800, Canada grew tobacco commercially. In 1862, the USA devised its Federal
Tobacco Tax to aid in finance for the Civil War.(4)
1900s
An important event took place at this time in the states of US, the Tobacco War
i. The Tobacco War
During the early twentieth century, violence started in the tobacco belt of Kentucky
and Tennessee (US) as farmers tried to lessen their economic distress.The buyers of tobacco
had formed a trust called the ‘American Tobacco Trust’ formerly called as Duke Trust, which
was found by James Buchanan Duke in 1890 and were dominating the tobacco market by
simply buying tobacco from small companies and abolished his rivals.By the end of the
century this American Tobacco Trust sold upto 82 % of the tobacco products and became one
of the world’s richest men. In 1900 a farmer could earn from six to eight cents for a pound
leaf, after a few years the price dropped to two to three cents, because of the domination of

13
the American Tobacco Trust in the market. Due to this the farmers were unable to make a
living, banks and businesses that relied on these farmers went down.(5, 6)
On September 1904, Felix Ewing a businessman from Tennessee and Joel addressed a
gathering of about 1,000 farmers and formed an organization to fight against the trust. They
formulated a charter and called it as "The Planters Protective Association". About 5,000 new
members joined the association within a few days. The objective of this Association was to
offer better prices for the crops by pooling them and fixing the prices. (7, 8)
Many farmers refused to join this association as they were paid great prices by the
American Tobacco Trust in an attempt to break the association and they were called as
‘hillbillies’. There was a great deal of friction between these two groups of farmers. The
initial efforts of the Planters Protective Association were lead by David Amos and were
meant to get more leverage for farmers in opposition to the American Tobacco Trust to get
some economic control over the lives of the farmers. Amos had a tight focus on the activities,
by organizing night raids on tobacco warehouses, in order to show the strength of local
farmers from Kentucky and Tennessee.(5, 8)
Night riding began in an attempt to force the others to come into the farmers
Association. They destroyed hillbillies’ farming by destroying the seed beds, spraying
kerosene and igniting it sowing the beds with salt. During these events, in the tobacco
warehouse, of a prominent hillbilly planter, the doors where the tobacco was heaped inside
were soaked with kerosene and sticks of dynamite hurled inside. Within moments the
building exploded which was glaring and ear splitting. Thus, making nearly 10,000 men to
join the association.(7)
The then US President Theodore Roosevelt prohibited anti-competitive business
practices and declared American Tobacco Trust as unconstitutional. In 1906, the Planters
Protective Association formed with the official name of "The Silent Brigade". It was a series
of events, not a single one and not an organized response under a single leadership. It was a
period where a number of issues came to occur in Kentucky.The participants in these
violence came to be known as the tobacco night riders. These acts of violence collectively
came to be known as the Black Patch War. The Black Patch referred to the region of the
Kentucky and Tennessee which are noted for the growth of dark-fired tobacco.(6)

14
Figure 1: Tobacco Warehouse
Figure 2: Night riders
Figure3: Quotes of warning from the Night riders

15
1950
In 1950 Doll and Hill from UK & Wynder and Graham from USA had published their
first major reports on smoking stating that smoking causes lung cancer. In 1962, the British
Royal College of Physicians of London, UK published a Report on Smoking and its health
effects. In 1964 USA Surgeons General’s Report stated that smoking causes lung cancer in
men.(4)
ii. Tobacco As A Custom
Tobacco is an important plant to Native Americans. They used tobacco for prayer,
protection and healing. They have used it for ceremonies, such as rituals that bless the house
and family. (1, 9)
Santo Domingo Tobacco, is traditionally used by priests in rain ceremonies, by mixing
with herbs whose smell are believed to be sacred. This mixture is smoked in a clay pipe or
corn husk (outer membrane of fruit). By blowing smoke, it is believed that the powers that
send the rain is gained.(10)
In US, tobacco was used as a custom in order to promote the community, spiritual, and
emotional well-being. It was used as an offering to the God, to persons and place. A gift of
tobacco was considered as a sign of respect and was also offered when asking for guidance,
help or protection. In many teachings, the smoke of tobacco was believed to carry thoughts
and prayers to the God. (9)
II. INDIAN HISTORY OF TOBACCO
1500s, 1600s
In India, tobacco was introduced by European travellers, especially by the Portuguese
during the period of Akbar (1550 to 1605). The plant was first cultivated in the state of
Gujarat, followed by Andhra Pradesh before 1600. By 1617, tobacco usage became
widespread, even among the common people. In the Golkonda kingdom (1618 to 1622),
much of the cultivated tobacco was exported to Mocha and Arakan. By 1630, tobacco were
exported by about 500,000 pounds and contributed good revenue to the government.(11)
During 1669 to 1679, tobacco was included in the gift items given to the holy men.
On the Coromandel Coast, tobacco was used to be served with betel leaves and areca nut at

16
all Hindu weddings. The natives of India smoked tobacco so much that their children of age 3
or 4 years frequently intake it, and it is made frequent amongst them.(11)
1700s
In the year 1787, the Royal Botanic Garden was established which is known today as
“Calcutta Botanical Garden”. The garden is one among the oldest gardens in Asia, and was
established by the East India Company, which was mainly planned for the purpose of
increasing the revenue of the company. In addition to Tobacco, other plants such as
cardamom, clove, cinnamon, black and white pepper were also cultivated for commercial
purposes.(12, 13)
1900s
In order to endorse and organize agricultural research all over India, a Council was
proposed by the Royal Commission on Agriculture to guide research activities. In 1903,
‘Imperial Agricultural Research Institute’ was initiated which is presently known as ‘Indian
Council of Agricultural Research’ (ICAR). (13)
The Government of India also established a Tobacco Board in place of “Tobacco
Export Promotion Council” under the Tobacco Board Act of 1975, in order to regulate and
facilitate production and promotion of tobacco in overseas market and control the imbalance
between supply and demand. (13)
2000s
Now, tobacco is one of the important cash crops of India. According to the WHO
report, annual production of Flue Cured tobacco increased in 2017-18 to around 239.05
million kg as against 204.07 million kg produced during the previous year. In the year 2020 -
21,the gross national income is about 1981 crores. Tobaccos offer significant employment
opportunities to both in-farm and out-farm situations. The prime beneficiaries of tobacco
trading are small and marginal farmers, rural women and tribal youth.(14)

17
TYPES OF TOBACCO
I. BOTANICAL TYPES OF TOBACCO
The genus Nicotiana is one of the genera of Solanaceae, about 70 species are recognised and
are grouped in the following sub-groups: (3,15, 16, 17, 18)
Nicotiana rustica
Nicotiana tabacum
Nicotiana petunioides
Among the 70 species, Nicotiana tabacum and Nicotiana rustica are cultivated the most.
Some of the common species of tobacco are listed below: (15)
Nicotiana alata (Indian tobacco, Flowering tobacco, Ornamental
tobacco, Winged tobacco, Jasmine tobacco)
Nicotiana attenuata (Coyote tobacco)
Nicotiana clevelandii ( Cleveland's tobacco)
Nicotiana excelsior
Nicotiana forgetiana
Nicotiana glauca (Tree tobacco, Glaucous tobacco)
Nicotiana glutinosa
Nicotiana langsdorffii (Langsdorff's tobacco, Fumo-bravo )
Nicotiana longiflora ( Long flower tobacco)
Nicotiana obtusifolia (Desert tobacco)
Nicotiana paniculata
Nicotiana plumbaginifolia (leadwort-leaved tobacco)
Nicotiana quadrivalvis ( Indian tobacco)
Nicotiana repanda (Fiddle leaf tobacco)
Nicotiana rustica ( Aztec tobacco )
Nicotiana suaveolens ( Australian tobacco )
Nicotiana sylvestris ( South American tobacco )
Nicotiana tabacum
Nicotiana tomentosa
Nicotiana velutina ( Velvet tobacco)

18
Figure 4 : N. tabacum
II. COMMERCIAL TYPES OF TOBACCO:
Based on usage tobacco is classified as:
i. Smoking tobacco
ii. Smokeless tobacco
i. Smoking Tobacco:
Smoking tobacco is characterized by burning of the tobacco, and the smoke that is created
can be inhaled or is held in the mouth. In some regions, ‘reverse smoking’ is observed, where
the burning end is placed inside the mouth.

19
The following are the different forms of smoking tobacco:(19 - 23)
a. Cigarettes
b. Cigars
c. Cheroots
d. Bidis
e. Kreteks
f. Pipe smoking
g. Water pipes
h. Sticks
a. Cigarettes:
The major components include tobacco, filter and paper wrapping.(19)
Cigarettes consist of shredded tobacco leaves processed with chemicals in it. They can be
made with or without filter; the popular most are with filter-tips, which are usually made by
machine. Another important segment is Roll-Your-Own (RYO) cigarettes, these hand rolled
cigarettes are also used worldwide.(20)
Cigarettes are available throughout the world and constitute the predominant form of tobacco
product globally. About 80 % of the global tobacco grown is used for cigarettes. (19)
Electronic Cigarettes:
Also called as Vape Pen, Hookah Pen, e-Hookah
These Electronic Cigarettes often resemble traditional cigarettes but their heat source is
usually by battery. It contains a liquid that holds nicotine and flavourings and this liquid is
called as e-liquid. The battery is turned on to convert the e liquid into aerosol that is inhaled
by the user. (19, 20)
b. Cigars
It comprises of air cured and fermented shredded tobacco particles wrapped in a tobacco leaf
or other wrapping substance, the tobacco wrapper. (19, 20)

20
It comes in different flavours for attracting younger population, with many sizes and shapes
from smaller ones called as little cigars, or cigarillos to larger ones called as premium cigars,
10 gram cigars called as double corona cigars. (20, 21, 22)
Regional variations of cigars are the Stumpens and Cheroots used in Western and Central
Europe and the Dhumtis, the conical cheroots used in India. The larger ones are equally
harmful in producing 10 times the nicotine and 5 times carbon monoxide than a filtered
cigarette. (20, 22)
Cigars are available throughout the world.(19)
Cigars were initially thought to present with comparatively little harm than cigarettes, though
it is a misconception, because it can be as equal as or more harmful than the usual filtered
cigarettes. It is also an illegal product circulating in the market.(19, 20)
c. Cheroots:
They are smaller cigars made of heavy-bodied tobacco. They are not wrapped by wrapper
rather contain a single binder. (20, 21)
d. Bidis:
They consist of small amounts of tobacco with flavouring agents packed along with it and
wrapped in a non-tobacco leaf called as tendu or Tembruni and are tied with small
strings.(19,21)
Bidis are found thoughout South East Asia, and are more popular in India. Once, the sales of
bidis were 8 times than that of the cigarette. In India bidis are mostly hand rolled and
manufactured in small scale cottage industries.(19)
Though they are smaller in size, their carbon monoxide and tar deliveries can be greater than
the manufactured cigarettes due to the need to puff harder to keep bidis lit.
e. Kreteks:
They are also regional products whose origin is in Indonesia and so the popularity. It is a
cigarette like product made of tobacco, cloves, cocoa and other flavouring agents wrapped in
paper. They contain a wide range of flavourings most often the clove and the eugenol in it has
an anaesthetising effect allowing deeper inhalation of smoke. Here, it is mostly manufactured
by machine.(19, 21)
f. Pipe smoking:

21
Pipe smoking is one of the oldest forms of smoking. They are smoked all over the world but
they differ in size, shape and the material used which include slate, briar, clay or other
substances . In one form, the tobacco is kept in the bowl and is inhaled through the stem,
sometimes through water. In Southeast Asia, clay pipes are used as the stem which is known
as chilum, suipa, and hookli. (21,22)
g. Water pipes:
Has a lot of names Shisha, Nargeela, Hookah, Narghile, Argileh, Okka, Boury, Hubble-
bubble, Kalian, Argeela, Sheesha, Ghelyoon, Ghalyan and Gouza. (19)
The shisha or hubble
bubble, are commonly used in the Mediterranean region, North Africa, and parts of Asia.(19)
The waterpipe works by placing the tobacco product in a bowl with pores in the bottom of it.
The bowl is attached to a tube linked with a water container. The tobacco leaves are heated
by hot charcoal which emits smoke. The water acts as a cooling agent and may actually
increase the harm by enabling water pipe smokers to inhale deeper into the lungs.Inhalation
of this toxic substance for an hour is as equivalent as 100 cigarettes. (14,23,24)
h. Sticks:
They are made from sun-cured tobacco known as brus and are wrapped in cigarette paper. (19)
Types of Tobacco Smoke:
Tobacco smoke comprises of the following:
➢ Mainstream smoke
➢ Side stream smoke
➢ Mainstream Smoke:
It is the direct smoke from the smoking tobacco (cigarette, cigar, pipes) that is inhaled by the
smoker.(25)
➢ Side Stream Smoke:
It is the smoke from the smoking tobacco (cigarette, cigar, pipes) along with the surrounding
environmental particles. It is the combination of the smoke that is exhaled by the smoker, the
smoke from the smoking tobacco and surrounding air.(25, 26)

22
Figure 5 : Roll-Your-Own (RYO) cigarette
Figure 6:Women smoking large cigar,Figure 7:Women smoking Cheroot
Figure 8: Kretek, Figure 9: Pipe smoking

23
Figure 10: Water pipe
ii. Smokeless Tobacco (SLT):
Smokeless tobacco is the tobacco that is consumed without burning.
The main forms of Smokeless tobacco:
a. Chewing tobacco: Betel quid (Paan, Gutkha, Gudakhu, Khaini, Pan masala,
Mawa, Mishri, Zarda, Naswar, Shammah, and Toombak)
b. Snuff: (dry and moist snuff)
c. Dissolvable products
d. Snus
a. Chewing tobacco:
➢ Betel quid:
Betel quid is a form of smokeless tobacco containing betel leaves, slaked lime, areca nut and
tobacco with flavouring agents like cinnamon, cloves. Other forms of quid with a little
variation in composition are Paan, Gutkha, Gudakhu, Khaini, Pan masala, Mawa, Mishri,
Zarda, Naswar, Shammah, and Toombak.(19, 27, 31, 32)
This form is popular in South and South East Asia.(19)
▪ Paan – comprises of betel leaves, areca nut, slaked lime and catechu, tobacco. (19, 21, 27,
30)
▪ Gutkha – made of areca nut pieces coated with powdered tobacco, flavoring agents,
and other ingredients that has the potential to increase the addiction.( 27, 30)
▪ Gudakhu– is a paste of tobacco and sugar molasses mixture. ( 27, 30, 32)
▪ Khaini- composed of dried tobacco leaves which are crushed and mixed with slaked
lime(27, 31)

24
▪ Pan masala is a mixture of areca nut, catechu, slaked lime, and condiments, along
with powdered tobacco. (27, 28, 29, 31)
▪ Mawa is a combination of areca nut pieces, aromatic tobacco, and slaked lime that is
mixed whenever necessary and chewed as a quid.(27-30)
▪ Mishri, are roasted tobacco powder that is used as toothpowder because it is believed
among the people that it has germicidal effects and helps in cleaning the teeth.(29)
▪ Naswar, is a mixture of sun-dried, and powdered local tobacco, flavouring and
colouring agents, slaked lime, ash and oil. The mixture is rolled into balls and is
usually placed under the tongue and sucked. It is used widely in Afghanistan,
Pakistan, Iran and the central Asian Republics.(27, 28)
▪ Shammah - a mixture of powdered tobacco, black pepper, lime, ash, oil and
flavouring agents. It is used in the Middle East, Saudi Arabia and Yemen.(28)
▪ Toombak- consists of four parts of tobacco with one part of sodium bicarbonate. It is
primarily used in Sudan. (27, 30)
b. Snuff:
Another form of smokeless tobacco comprising shredded or powdered tobacco leaves.
There are two Types of snuff:
➢ Dry snuff
➢ Moist snuff
➢ Dry snuff is a mixture of dried tobacco powder and aromatic chemicals.It is inhaled
through the nose and is found to be more common in European countries.(19, 21, 27, 30)
➢ Moist snuff – comprises of Pulverized tobacco that are fermented and packed. They
are placed in the vestibule between the lip or cheek and the gingiva and are spitted out
after a while. This form of tobacco is popular in US and Scandinavia.(19, 21, 27, 30)
c. Dissolvable products:
It can be attributed as a form of smokeless tobacco, which are sold as lozenges, strips, sticks,
or even may look like a candy with flavourful agents. Its nicotine content can cause
addiction.(19, 21, 27. 28, 29)
d. Snus:

25
Snus is a finely grinded moist form of non-fermented tobacco product. The snus is available
as packets or pouches. The pouches are placed most commonly in the vestibular region of the
upper lip. They are kept in the mouth for about 15 minutes to 1 hour, after which it is
disposed. It is separated from smokeless tobacco list as it need not be spitted. (19, 21,27, 30)
Figure 11: Betel quid
Figure 12: Paan
Figure 13: Gutkha, Figure 14: Man ingesting Gutkha

26
Figure 15: Gudakhu
Figure16: Khaini, Figure 17: Khaini mixed with slaked lime
Figure 18: Moist and Dry snuff, Snus

27
TOBACCO CULTIVATION AND PROCESSING
I. CULTIVATION OF TOBACCO:
Tobacco seeds are planted in masses, the cultivation of tobacco has to undergo various
processes before it is ready for market.
Due to the different conditions of the type of soil, climate, rainfall, irrigation, fertilizers
and the pesticides in the diverse tobacco growing locations, the tobacco leaves can vary in
size, colour and flavour. Also various factors during harvesting, curing, handling and
processing influence the quality of the leaf and ultimately the product manufactured.The
quality of the leaf is determined by its colour, texture, thickness, strength, aroma, flavour and
processing qualities. The Quality is expressed in grades. The US Department of Agriculture
(USDA) recognizes 117 levels of grades for tobacco. ( 2, 12, 32, 33, 34)
i. Climate And Soils:
To grow tobacco, 15-20 degree Celsius temperature and 50 to 100 cm of annual rainfall is
required. Tobacco plants cannot stand if the rainfall is more than 100 cm. After harvesting to
drying the leaves, the plant requires dry weather and good sun, but not less than 8%
moisture.(33)
Different types of soil are required for different types of tobacco. For instance, Bidi
tobacco requires alluvial soils, loamy soils or black clay soil, Cheroot and cigar tobaccos
require grey to red soils varying from light gravelly to sandy loams. (33)
ii. Various Types Of Tobacco Cultivated In India(34)
In India, tobacco is grown in about 15 states which includes Andhra Pradesh, Assam,
Bihar, Chattishgar, Gujarat, Karnataka, Madhya Pradesh, Maharashtra, Odisha, Tamil Nadu,
Telangana, Uttar Pradesh, West Bengal. The important types of tobacco in India include flue-
cured tobacco, country tobacco, burley, bidi, rustica, hookah, cigar-wrapper, cheroot,
Oriental, HDBRG, burley, Lanka, Pikka, Natu and chewing tobacco. (11, 13, 15, 43 )
Flue Cured Virginia (FCV), Burley and Oriental tobacco account for the major
exportable tobacco types. India grows N. tabacum extensively in most areas of the country.
The N. tabacum varieties called as desi types are developed for cigarette, cheroot, cigar, bidi,
hookah and snuff tobaccos.(13)

28
N. rustica requires cool climate, so its cultivation is limited mainly to the north and
north-eastern areas of the country, which includes U.P., Bihar, West Bengal and Assam.
The N. rustica, known as `vilayati' and `calcuttia' are developed for only chewing and snuff
tobaccos. In addition many species of Nicotiana, such as N. affinis, are grown as ornamental
plants. There are about 70 Nicotiana Sp. available in the world, of which 45 can be found in
India.(44)
Table 1: Smoking tobacco - Flue-cured tobacco
S.NO. Variety, Year of release
1. Chatam, 1950
2. Delcrest, 1960
3. Kanakaprabha, 1971
4. Dhanadayi, 1972
5. CTRI Special, 1976
6. 16/104, 1976
7. FCV Special, 1976
8. Jayasri, 1979
9. CTRI Spl. (MR), 1980
10. Godavari Spl. , 1982
11. Swarna, 1984
12. Mc Nair 12, 1986
13. Jayasri (MR), 1986
14. Hema, 1987
15. Bhavya, 1988
16. Gauthami, 1992
17. CM 12 (KA), 1993
18. VT 1158, 1993
19. Kanchan, 1998
20. Thrupthi, 1998
21. Rathna, 2001
22. 222, 2012
23. CH-1, 2015
24. N-98, 2015

29
25. LT Kanchan, 2015
26. CH-3, 2016
27. CTRI Sulakshana (TBST-2), 2018
28. FCJ-11 , FCR-15 2019
Table 2: Smoking Tobacco - Bidi
Sno Variety, Year of release
1. GT 4, 1976
2. NPN 190, 1979
3. Anand 119, 1984
4. Anand 2, 1984
5. Spoorthy (PL 5), 1984
6. GT 5, 1985
7. GT 7, 1993
8. GTH1, 1995
9. Bhavyasree, 1997
10. GT 9, 2001
11. MRGTH-1, 2008
12. ABT 10, 2009
13. Vedaganga 1, 2009
14. GABT-11, 2013
15. Nandyala Pogaku-1, 2015
16. NBD-209, 2016
17. ABD-132, 2019
Table 3: Chewing Tobacco
SNo. Variety, Year, Region
1. Chama, 1956, West Bengal
2. Podali, 1956, West Bengal
3. DP 401, 1958, Bihar
4. Gandak Bahar, 1976, Bihar

30
5. Sona, 1977, Bihar
6. Vairam, 1977, Tamil Nadu
7. Thangam, 1980, Tamil Nadu
8. Bhagyalakshmi, 1980, Tamil Nadu
9. Maragadham, 1981, Tamil Nadu
10. Prabha, 1981, Bihar
11. PT 76, 1990, Bihar
12. Meenakshi, 1992, Tamil Nadu
13. Vaishali Special, 1993, Bihar
14. Lichchavi, 2001, Bihar
15. Manasi, 2004, West Bengal
16. Abirami, 2006, Tamil Nadu
17. Kaviri, 2006, Tamil Nadu
18. Meenakshi (CR), 2007, Tamil Nadu
19. Sangami, 2008, Tamil Nadu
20. Kamatchi (VDH 3), 2013, Tamil Nadu
21. Abirami (CR), 2013, Tamil Nadu
22. DJ-1, 2013, West Bengal
23. BSR-1, 2014, Tamil Nadu
Table 4: Miscellaneous:
SNo Type of tobacco Varieties
1 Hookah and Chewing
(rustica) tobacco
DD 437, Sonar Motihari, GC 1, GT 6, GCT 2, GT 8, GCT
3, Dharla, Azad Kanchan
2 Motihari tobacco Manasi, Torsa
3 Natu tobacco Prabhat, Vishwanath, Natu Special, Gajapati, Bhairavi
4 Cheroot tobacco DR 1, Bhavani Special, Lanka Special, Sendarapatty
Special
5 Cigar-wrapper
tobacco
S 5, Krishna
6 Burley tobacco Burley 21, Banket A1, HDBRG (Dark burley)

31
iii. Steps In Tobacco Cultivation:
Generally, tobacco cultivation consists of the following process:
a. Raising seed beds:
Since the seeds are very small and fragile, it must be raised in seedbeds before being planted
in the field.
b. Suckering:
As the crop grows, suckers are removed and the process is called suckering.
The suckers are the side shoots which grows once the flower of the plant is picked. They are
removed since they will utilize more of water and minerals from the plants which can lower
the quality of the leaves. They can be removed either by hand or by using chemicals. This is
done at the time of harvesting or during the earlier stage of growth. (2, 35)
c. Harvesting:
As the leaves reach the desired size, they are collected together, and this process is known as
harvesting. The harvesting time for each type of tobacco differs.
Harvesting time of some types in India :(33)
FCV tobacco – December to March in Andhra Pradesh and July to September in Karnataka.
Bidi tobacco - January to February
Cigar and Cheroot tobaccos - 90 to 100 days after planting when the leaves become brittle
and yellowish green.
Chewing tobacco – 110 to120 days after planting when the leaves develop puckering
Hookah tobacco (rustica) - May or June, when broad flecks appear on the leaves.
d. Priming:
Certain types of tobacco (Flue cured, oriental tobacco) are harvested in stages as the leaves
ripen and they are not removed all at once. This process is called priming.(35)
I. PROCESSING OF TOBACCO:
After harvesting, processing of the plant is done to obtain the final tobacco product.

32
i. Curing:
Curing is the procedure of drying or reducing the moisture content on the leaves for
processing it further. (32, 35)
Curing is of four methods:
a. Air curing
b. Flue curing
c. Fire curing
d. Sun curing
a. Air curing
Air curing is done in barns in which the leaves are stacked in bundles and hung for
curing by natural heat. Air cured tobacco will be brown in colour.(2, 35)
b. Flue curing:
In Flue curing, artificial heat is the main drying source obtained by oil or petroleum. It is
required in humid conditions. The curing barns contain pipes for letting in heat and fans for
dissipating the heat to the entire barn. Curing of unstringed leaves in bulk is termed as bulk
curing, done in bulk barn for tobaccos that require a great amount of artificial heat. Here the
tobacco is yellow to dark orange in colour and is referred to as virginia tobacco. (2, 35)
c. Fire curing:
Exposure of tobacco directly to heat and smoke in open fires is involved in fire curing,
here the smoke alters the taste of the tobacco. (35)
d. Sun curing:
In Sun curing the tobacco leaves are exposed to sunlight. (35)

33
Figure 19 : Tobacco cultivation
Figure 20: Steps in cultivation of tobacco plant
Figure 21: Air curing , Figure 22: Fire curing

34
Figure 23: Flue curing, Figure 24: Sun curing
ii. Picking:
After curing, picking is done which is the removal of non-tobacco related materials
and undesirable leaves from the tobacco plant.(35)
iii. Threshing:
After picking, the blade of the leaves are cut away from the stem with a machine
called thresher, which results in smaller pieces of leaf blade which are suitable to use in
cigarettes. This process is called threshing .(35)
iv. Blending:
Blending is the process of mixing different types of tobacco in a predetermined ratio
to obtain a flavourful content.(2)
v. Re Drying And Packing:
The blended tobacco is again dried and then packed, stored and transported to various
tobacco sellers.(35)

35
Figure 25: Curing methods of tobacco
Figure 26: Steps in processing of tobacco

36
COMPONENTS AND PHARMACOLOGY OF TOBACCO
I. COMPONENTS OF TOBACCO:
In 1981, the World Health Organization stated that the leaves of tobacco contain high
amounts of protein, amino acids like lysine, and no nicotine. K.H. Ginzel stated to WHO that
young tobacco plants can yield the most superior plant protein, the Fraction-1-protein (F-1-p)
which is colourless, tasteless, odourless and can be obtained in pure crystalline form from the
plant. The functional characteristics of this protein can be superior to soy protein, animal
proteins including from egg white and casein. The protein is said to have an optimal amino
acid which has the ability to lower the cholesterol.(36)
The efficiency of F-1-p was identified superior to soy, corn and casein through
experiments. It is also said that it can be used for renal dialysis patients and as artificial milk
for infants. F-2-proteins (mixture of low molecular weight soluble proteins) from tobacco can
also be added to the beverages and is considered to boost up the nutritional quality. (37, 38)
The Leaf Protein International demonstrated the extraction of crystalline F-1-p in 1981. It
stated that tobacco plants can generate four times more protein per acre as of soybeans and
corn with a yield of F-1-p of 600 kg/ha.(36)
It also stated the nicotine concentration of the
leaves is 20 ppb, which is lower than tomatoes, potatoes or green peppers. (36)
Mendel and Vickery stated that immature seeds of tobacco contained small fractions of
alkaloids. Then nicotine was detected in the sprouts and cotyledons after 9 to 11 days
germination. However the investigators showed later that this has little or no effect on the
nutritive properties of the seed. Lapayette B. Mendel stated that they could not demonstrate
the alkaloid content in tobacco seeds. (39)
Paolo Fantozzi et al in 1983 stated that the digestibility of the protein from tobacco was
highest among the vegetable protein sources. He also stated that by using high level of
nitrogen fertilizer and more planting, high yields of protein upto 1794 Kg/ha can be
obtained.(40)
M Parameswaran et al in 1988 evaluated the total Protein concentrate of the tobacco
leaves by heat coagulation method in bidi tobacco and demonstrated 52% of protein, which
was free from nicotine. He fed 25% of the dietary protein supplement with this tobacco

37
protein to the albino rats and observed its growth to be comparable with the control
animals.(41)
The Nicotine Content:
Nicotine, an alkaloid is produced by the plants of this nightshade family, though not by
every plant of this family. The species of this family containing traces of nicotine are Atropa
belladonna, Datura stramonium, Duboisia myoporoides and the edible plants like potatoes,
tomatoes, eggplants, Capsicum. The sprouted areas of potatoes contain more nicotine than the
usual amount. Cooking reduces the amount of nicotine by half. The tomatoes contain less
nicotine as they ripen.Nicotine content in the leaves of N. tabacum is 1-3%, N. rustica
contains up to 9% nicotine.
II. PHARMACOLOGY OF TOBACCO:
Nicotine being the main component and of significance in tobacco, it is considered here.
Nicotine, acts in a biphasic way: it causes stimulation in low dosage and sedation in high
dosages. In lower concentration, nicotine is said to promote the release of numerous
hormones and nerve transmitters like dopamine, adrenaline, norepinephrine. These further
cause increased heart rate and blood pressure by constricting the blood vessels (especially the
peripheral).(42)
Liver releases glucose for rapid availability to the motor muscles. Blood sugar levels are
increased which may be due to the blocking of insulin, which causes a feeling of satiety or
absence of hunger. Increase in the feeling of sharpness, alertness, may be observed which are
similar to those caused by psychostimulants. If nicotine concentration in blood is higher,
these stimulating effects are short lived and are replaced by sedative and pain-reducing
effects. Anxiety will be reduced and the user experience feeling of relaxation. Dopamine is
increased, creating reward systems in the brain, a cause of addiction.(42)

38
IMPACT OF TOBACCO
The consequences encountered due to tobacco usage can be broadly categorised as: (42)
I. Economy
II. Environment
III. Health
The impact of tobacco on economy and environment are briefly discussed here. As
tobacco and health is the topic of concern in this book, impact on health is discussed in detail
in the next chapter.
I. IMPACT OF TOBACCO ON ECONOMY:
The tobacco smoking not only takes the health of the smoker but also his wealth.
According to WHO, about 5 to 15% of a smoker’s income is spent on tobacco products,
which can be a huge economic burden on them and their family. (42)
In India 2011, the total economic cost attributable to tobacco consumption for middle-aged
group from all diseases was about US$22.4 billion. Direct medical costs for hospital care and
treatment of tobacco related diseases amounted to US$3.6 billion. The indirect morbidity cost
is about US$3.1 billion. 91% of the Males contributed to this economic burden and the
remaining accounted were females. Among the females, SLT accounts for about 66% of
direct medical costs. SLT has a tax of about 75% across India. In the past decade, excise
revenue from tobacco has increased enormously. Although the Government of India is trying
to increase taxes for SLT products, still the gross revenue is less than 1%.
The average expenditure by a person in buying cigarettes and SLT products is higher in
urban than in rural counterparts (in the case of bidis). The highest amount of money is spent
in buying cigarettes then SLT followed by bidis. Money spent in buying cigarettes is Rs.
12.60/- and for SLT is Rs. 8.50/-. (46)
Corsi and Subramanian in 2014 assessed the socioeconomic inequalities in smoking
behaviour among the males of India and stated that wealthier, educated, a decent job people
were more prone to cigarette smoking. On the contrary, less educated people with poor
socioeconomic status had a habit of bidi smoking. This unusual variation in socioeconomic
gradients in consumption of two smoking habits has been reported among the males.(46)

39
i. Reasons For Producing Tobacco Plants:
a. Tobacco is one among the most economically significant crops in the world.
b. It is drought resistant
c. Takes only a short duration to grow
d. It can be cultivated on soils where other crops cannot be cultivated profitably.
For many decades there was a steady growth in tobacco production but in the 1990s
the world demand for tobacco products came to a pause. Demand from the developed
countries declined, in less developed countries the growth has slowed down. This pause is
due to many facts such as diversification, litigation and consolidation. (32)
Consolidation has prevailed for many years but over ruled in 1990s, due to the
stagnation of demand for tobacco; the small companies were not able to survive by the
manufacturing and distributing of the products and other marketing processes. This caused
merging of the larger companies with smaller companies so that high volumes of tobacco can
be obtained from fewer locations. The private companies were absorbed by multinational
companies. Thus in 1999s, the companies British American Tobacco (BAT), Philip Morris
and China National Tobacco Corporation (CNTC) dominated the production of global
cigarette which accounts two-thirds of production. These situations had unpleasant effects on
the tobacco suppliers as well as the leaf producers, dealers, machine workers, paper
suppliers.(32)
In 1990s China produced 30 % of world tobacco. 12 % of the total is occupied by the
United States making it the world’s second largest producer. Other principal suppliers of
tobacco include Japan, Indonesia, Brazil and Germany. (32)
According to the WHO, in 2000, the production of tobacco globally was nearing 7
million metric tons, which was more than double the amount of production since 1960s.
Tobacco plant was grown in about 125 countries, the land occupied for cultivation of the
species is over 4 million hectares, one third of this entire land belongs to China. Tobacco
accounts less than 1 % of the global agricultural land. Lands attributed to cultivation belongs
to China majorly then comes the USA, Canada, Mexico, Malawi and United Republic of
Tanzania. Brazil, China, India, Turkey, USA together produce about two thirds of the global

40
tobacco. (43)
Other largest producers of tobacco includes Indonesia, Zimbabwe, Zambia,
Pakistan, Argentina(44)
ii. Tobacco Production In India:
In India, the important types of tobacco include flue-cured tobacco, country tobacco,
burley, bidi, rustica, hookah, cigar-wrapper, cheroot, Oriental, HDBRG, burley, Lanka,
Pikka, Natu and chewing tobacco. (11, 13, 15, 43 )
The major exportable tobacco types are the Flue Cured Virginia (FCV), Burley and
Oriental tobacco. (13)
There are about 70 Nicotiana Sp. available in the world, of which 45 can
be found in India. (44)
India grows N. tabacum varieties called as desi types extensively in
most areas of the country for cigarette, cheroot, cigar, bidi, hookah and snuff tobaccos.(13)
In the year 2016, India has occupied the second position in tobacco production and in
the following year it is pushed to the third position. (44)
In 2017, the leading tobacco producer
is China whose production is about 2.4 million tons, followed by Brazil producing 880.88
tons and then comes India whose production is 799.96 tons[19].
In exports, India ranked 3rd
with Brazil and USA ahead. Tobacco and its products earn about 20,000 Crores and 5000
Crores by foreign exchange. India is the 3rd
largest producer of Flue-Cured Virginia (FCV)
tobacco in the world. In India, production of FCV tobacco is about 240million Kg , which
accounts for around 30% of total tobacco produced in India. (44, 45)
According to Central Tobacco Research Institute (CTRI) 2020 report in India, tobacco
is grown in about 0.45 Million hectares producing approximately 750 Million kg of tobacco
leaves. India being the 3rd
largest producer and exporter globally after China and Brazil. The
production of FCV tobacco is about 300 million kg and non-FCV tobacco 450 million kg. In
the global market, Indian tobacco occupies about 10% of the area for cultivation and 9% of
the total quantity of tobacco production.(43)
It provides employment to 36 million people, including farmers, farm labourers engaged
in tobacco farming, people working in processing, manufacturing and exports. Bidi rolling
provides employment for 4.4 million people and tendu leaf collection is done by 2.2 million
tribes. Annually, tobacco contributes about 4,400/- crores for foreign exchange accounting
for 4% of the country’s agriculture exports and 14,000 crores to excise revenue which
accounts more than 10% of the total collection from all sources. (46)

41
During the past five years, exports of tobacco and its products is increased by 76% and
209%. Germany, UK, Belgium, the USSR, South Korea and South Africa are the major
importers of Indian FCV tobacco accounting for about 60% of our exports. India’s share in
world cigarette exports is less than 1%. However, the exports of scented Bidis and chewing
tobacco and zarda, Hookah tobacco paste are noteworthy. (46)
II. SOCIAL AND ENVIRONMENTAL CONSEQUENCES:
Tobacco Smoking affects both the social interaction and relationships. In most of the
cultures, people see smokers in a negative way (like smokers are smelly, disgusting, and
dirty). A smokers personal relationships can also be affected, as many people don’t consider
being in a relationship with a smoker. A smoker’s, child is more likely to smoke especially at
their younger age. (42)
i. Types Of Smoking:
a. First hand smoking
b. Second hand smoking
c. Third hand smoking
a. First Hand Smoking:
First hand smoking is the mainstream smoke that is inhaled by the smoker. The one
involved in this type of smoking is the smoker himself.
b. Second Hand Smoking:
It is the combination of both the mainstream and side stream smoke. If people inhale this
smoke then it is termed as passive smoking which is also called as involuntary smoking. Non-
smokers are more likely to experience this type of smoking. Though ignored, this type of
smoking is as harmful as first hand smoking.(25, 26,47)
c. Third Hand Smoking:
Third hand smoke refers to the second hand smoke residues that get deposited in the skin
surfaces and objects, furniture where a smoker lives. Infants, children’s are more prone to this

42
type of smoking as they meddle with objects and place it in mouths. The effects of third hand
smoking is not well recognised and is being studied.(47)
Burning of the tobacco produces a number of toxicants in the environment. The greater
use of fertilisers, pesticides and mechanisation, that contributed to the production of higher
yields are environmentally damaging. This problem doesn’t end with the growing tobacco;
the processes in curing the leaves can cause massive deforestation. Manufacturing, packing
and transportation of these products also cause environmental pollution.(42, 43)
In 2011, about 4 200 000 hectares of land were devoted for tobacco production,
representing less than 1% of total land globally; however, in many low- and middle-income
countries, the percentage of land devoted to tobacco production has increased. Deforestation
for production of tobacco has many environmental consequences – including loss of
biodiversity, soil erosion and degradation, water pollution and increase in atmospheric carbon
dioxide.
Tobacco production usually involves usage of chemicals (pesticides, fertilizers, growth
regulators). These chemicals may affect the drinking water sources as they can run-off from
the tobacco producing areas. Tobacco crops also deplete soil nutrients by taking up more
nitrogen, phosphorus and potassium than other crops. This depletion is compounded by de-
suckering the plants, which further increases the nicotine content and leaf yields of the
tobacco plants.
Farm workers, especially children, minorities and migrant workers are at risk of nicotine
toxicity (green tobacco illness), caused by handling of tobacco leaves without protection
during the harvest and processing.
In 1995, the global tobacco manufacturing produced about 2 000 000 tonnes of solid
waste, 300 000 tonnes of non-recyclable nicotine-containing waste and 200 000 tonnes of
chemical waste. If annual cigarette production had remained constant for the past 20 years,
the tobacco factories would have deposited a total of 45 000 000 tonnes of solid wastes,
6 000 000 tonnes of nicotine waste and almost 4 000 000 tonnes of chemical wastes during
this time. But the output has actually increased from 5 to 6.3 trillion cigarettes annually.
Other toxic by-products used in manufacturing include ammonia, hydrochloric acid, toluene
and methyl ethyl ketone.

43
Land used for farming in low- and middle-income countries tobacco cultivation can
be diverted as a cash crop. Intensive investments by tobacco companies (e.g. Philip Morris
International, British American Tobacco), leaf buyers (e.g. Universal Corporation and
Alliance One International) along with market liberalization measures have encouraged the
expansion of tobacco production in low- and middle-income countries. As a consequence
there are short-term economic benefits for farmers, but there will be long-term social,
economic, health and environmental detrimental effects.

44
IMPACT OF TOBACCO IN HEALTH
I. TRADITIONAL USES OF TOBACCO:
The tobacco plant was used as an orthodox medicine by the medical professionals.
Friar Ramon Pane, a Catalan priest on his journey observed and stated that in India the
powder was used by the medicine man to be grabbed with joy, after which he used to perform
a ritual for the sick men, by blowing on his temples, forehead and neck, and then declaring
that he had drawn out the sickness of the patient.(1)
Amerigo Vespucci, the Florentine navigator, wrote on his voyage to the New World in
1499, that he saw Indians on island of Margarita chewing leaves of a herb mixed with
pulverized lime to relieve thirst. (1)
Tobacco was considered to be the “God-sent remedy”.(1)
Tobacco were used in different
forms with different ingredients in different parts of the world for curing different diseases
and its symptoms. It was believed that tobacco has properties of antispasmodic, antiseptic,
narcotic, emetic, anti-diarrhoeic, emollients and anticonvulsant. Fernando Ocaranza wrote
that in 1519 the Indians were using tobacco as medicines for anti-diarrhoeic, narcotics, and
emollients.(1, 48)
In India, the leaves of tobacco were used in traditional medicine as a sedative,
antispasmodic, vermifuge, antiseptic, narcotic and emetic. In Malaysia, dried tobacco leaves
infusion was taken as sedative. (1, 48)
The traditional medicinal uses are as follows:
i. Respiratory disorders
ii. Gastrointestinal disorders
iii. Reproductive disorders
iv. Dermatological disorders
v. Infection and wounds
vi. Urinary system disorders
vii. Miscellaneous

45
i. Respiratory disorders
Monardes N in 1571 and Wateson G in 1598 described that finely grounded tobacco and
snuff, was used as a remedy for colds.(49)
Antonio De Herrera Y Tordisillas, a Spanish
historiographer, in his writing from 1601 to 1615 said that the tabaco cures pain caused by
cold; in smoke form it was also beneficial against asthma and coughs. It was described that
they used to place a cane about one foot long, one end at the nostril and through the other end
the powdered tobacco was placed to clear out the nasal passage.(1)
In Egypt, the dried leaves and flowers were smoked to relieve asthma. In Fiji, fresh roots
are taken orally for Asthma. In India, fresh leaves are mixed with cob of corn or
Amorphophallus paenoiifolius (the Elephant Yam) to treat asthma. (48)
In Haiti, dried leaves decoction was taken orally for bronchitis and pneumonia. In Peru,
the Jivaros and in Ecuador, the tobacco juice was used to treat pulmonary ailments.(48)
ii. Gastrointestinal Disorders:
Alonso Niffo in 1500 reported it to be used as a dentifrice.In United States the Native
Americans, mixed the tobacco with lime or chalks and used it as toothpaste to whiten the
teeth. In India, powdered tobacco was massaged on the teeth for this purpose and tobacco
toothpaste was also marketed commercially. (1, 48, 49)
In Guatemala, extract of dried leaf with hot water are applied externally for stomatitis.In
Asia, chewing tobacco was recommended for toothache and gum diseases, throat aches.In
India, exudate from the stems and leaves are used in cases of gingival inflammation. In
Nicaragua, leaves of tobacco were chewed for tooth ache. In Fiji, the seeds are taken orally
for treating hoarseness of voice.(48)
When babies suffer from stomach problems, the herb black wool, tobacco and the nest of
Cacicus chrysopterus, Icteridae, Aves (Birds) were fumigated around the cradle and anus of
the baby. In Brazil, the leaf juice was taken orally to induce vomiting &narcosis. In Papua
New Guinea, the tender leaves were chewed to relieve stomach ache. In Fiji, fresh roots of
the plant are taken orally for indigestion. (48)
In India, tobacco was traditionally used to treat strangulated hernia. In Asian countries,
decanted liquor of tobacco which was boiled, were used internally for treating indigestion,

46
aches in the belly.(48)
Pedro Alvarez Cabral, a Portuguese nobleman reported the herb was
used for treating fistulas, ulcerated abscesses, sores, uncurable polyps and other ailments. (49)
iii. Reproductive Disorders:
In Cuba, the extract of leaves was taken orally to treat the dysmenorrhea. In Mexico,
extract of the tobacco plant was massaged on the abdomen with saliva to ease the expulsion
of placenta. In Tanzania, the leaves are placed in vaginal region to stimulate labour. (48)
In Asia, tobacco with honey was used to treat syphilis.In Papua New Guinea, decoction of
tender leaves was taken orally for treating gonorrhoea. (48)
The inhabitants of Surguna in
Madhya Pradesh applied warmed leaves on testis to treat hydrocele.
iv. Neurologic Diseases:
In 1490s, in India the tobacco was used to prevent fatigue.(1)
In Fiji, fresh root juice was
applied for bloodshot eyes. In Kenya, water extracts are applied for corneal opacities and
conjunctivitis. (48)
Monardes N in 1571 and Wateson G in 1598 described that finely grounded
tobacco and snuff, was used as a remedy for headache and eye problems. (49)
In Nigeria, for
the treatment of convulsions, leaves were crushed and juice was collected which was used as
a bath in water.(48)
In Asian countries, Tobacco Smoke (TS) was passed into the ear to cure ear ache, tobacco
juice was put into the ears to improve deafness. In United States, the extract of the plants was
taken orally to treat tiredness. In Asian countries smoking tobacco was claimed to improve
body odour. Indians and Negroes powdered it in their mouths in order to fall asleep and feel
no pain. (48)
v. Dermatological Disorders:
In India, tobacco was traditionally used to treat skin diseases. In Iran, ointments made
from crushed leaves were used to treat baldness, dermatitis and Pediculicide. In Peru, the
Tikiana men and in Colombia, palm oil was mixed with crushed leaves as a hair dressing to
prevent hair loss. In Papua New Guinea, dried plants were mixed with bark of Gaibulima
belgraveana &Zingiber officinale (ginger) and taken orally for lice.(48)
In Nepal, tobacco leaf juice was applied externally to treat scabies. Ointment made with a
mixture of ashes of tobacco with pig fat was applied to ulcerated skin, warts, and dermal
cancer.

47
vi. Infection And Wounds:
In Colombia, Poultice prepared from fresh leaves was used over boils and infected
wounds. In Turkey, the leaves are powdered and were applied externally for wounds. In
Mexico the tobacco leaves are applied for pain relief, used in powdered form for the relief of
catarrh and applied locally to heal wounds and burns. In Guatemala, the leaves are applied
externally for wounds and extract of dried leaf with hot water are applied externally for
ringworms, bruises, sores, wounds and ulcers. (48)
The Tukanoan people rubbed a decoction of
leaves over sprains and bruises. In Nepal, tobacco leaves were applied locally for pain and to
heal wounds and burns.
In Egypt, the dried leaves and flowers are burned and smoked to relieve influenza. In
India, juice of Securinega leucopyrus was mixed with dried tobacco leaves and was applied
externally for parasitic infections. In East Africa, dried leaves and Securinega virosa are
mixed and used externally to destroy worms in sores.(48)
In Peru, the Jivaros used the tobacco juice for snake bite. In Nepal, hot water extract of
dried flower and leaves are used externally for snake and spider bite. In Argentina, tobacco
was applied for snake bites with milk and oil. (48)
In 1490s, tobacco herb was used by the Indians as disinfectant. In Brazil, dried leaves are
used as an insecticide. Tobacco was also used to treat distemper, a viral infection in animals
with cooking oil and milk. Onion, lemon, and tobacco mixture with white soap and warm
water were used to treat scabies.(48)
vii. Urinary System Disorders:
In Guatemala, the leaves were taken orally for kidney diseases. In Asian countries,
decanted liquor of tobacco was boiled and used internally for treating urinary tract
obstruction. Tobacco Smoke (TS) when applied to the anus relieved constipation and bloody
discharge.
viii. Miscellaneous
In Egypt, tobacco leaves are used as a poultice along with oil to treat rheumatic pain. In
India, decoction of leaves was applied for muscle relaxation, also to relieve pain and swelling
associated with rheumatic conditions. In Fiji, the seeds are taken orally for treating
rheumatism.(48)

48
In Nepal, tobacco was used in powder form to relieve catarrhal conditions. In China the
people of Lop Nur used tobacco along with Apocynum venetum (sword-leaf dogbane plant) as
it’s leaves were believed to have low tar content and hence used as an agent to detoxify the
nicotine content.
II. DETRIMENTAL EFFECTS OF TOBACCO ON HEALTH:
As time went, it was recognized that tobacco was not a cure for all ailments. In 1601,
anonymous pamphlets were released, in London. This pamphlet described that tobacco was a
poison and stated that tobacco was harmful because it deprives the body nourishment, dries
up men’s sperm, and had a stupefying effect. It also added that tobacco should be avoided
especially by young people and pregnant women. (49)
In 1604, King James I from England stated a warning that smoking was injurious to the
brain, eyes, nose, and lungs. In 1620, Thomas Venner from London wrote that excessive use
of tobacco harms the brain and sight, diminishes digestion, and induces palpitation, shaking
of the limbs. He said that tobacco should be limited to medicinal use and not for pleasure.
After this, many reports were established stating other diseases caused by tobacco. And
despite the warnings about the possible harms that tobacco may induce on its abusers, it took
nearly 450 years to distinguish the consequences of tobacco usage. (49)
Tobacco Abuse
The tobacco products contain about 5000 toxic substances in it.(42)
Among which the most
important and dangerous constituents are:
➢ Nicotine
➢ Carbon Monoxide
➢ Tar
➢ Carbon dioxide
➢ Nitrogen oxides
➢ Hydrogen cyanide
➢ Ammonia
➢ Volatile nitrosamines
➢ Volatile hydrocarbons,
➢ Volatile sulfur containing compounds
➢ Aldehydes

49
➢ Ketones
Nicotine:
Nicotine is an important and major cause of behavioural effects of the tobacco. It is a
poisonous substance that leads to addiction influencing and reinforcing the tobacco use
behaviour.
Nicotine has a structure similar to the neuro-transmitter acetylcholine (Ach) that
conveys information from one neuron to the other. The Ach is an important neurotransmitter,
which is involved in systems that concerns with learning and memory, mental and physical
arousal, and other aspects of emotions. The Ach receptors throughout the body that respond
to nicotine are called as nicotine receptors. The nicotine thus combines with Ach receptors
and exerts actions similar to Ach at all the areas where nicotine acetylcholine-receptors are
present and can trigger impulses.(42)
After absorption, nicotine binds to receptors in the brain thereby influencing the
cerebral metabolism. It reaches the brain rapidly (in seconds) and hence, the smoker gets
these psycho active rewards very quickly within seconds of smoking. It is then distributed
throughout the body, especially to the skeletal muscles. (42)
ii. Health Effects Of Smoking Tobacco
Tobacco is deadly in any form. Tobacco smoking is the leading cause for premature
death of approximately 6 million people worldwide (Action on Smoking and Health, 2016;
World Health Organization, 2013). The premature death due to smoking is deﬁned as a form
of death, in an individual due to a smoking-related disease otherwise whose death would have
later been for another cause. Globally, over 22 000 people die from tobacco use or
secondhand smoke exposure every day and one person is lost for every 4 seconds stated by
the WHO, 2019. (25)
Smoking tobacco products, contains about 7000 chemicals, at least 250 chemicals are
known. Some among these compounds can cause cancers of various organs in the body. It is
found that the smoker who does not stop smoking loses 10 years of an average of life
expectancy when compared with non-smokers and they suffer diseases around 10 years
earlier than non-smokers (Jha &Peto, 2014). Smokers, after the age of 40 have higher levels

50
of pain and disability than non-smokers (US Department of Health and Human Services,
2004). (50)
Another entity apart from the conventional cigarettes is the cigar. It has been found
that more young adults, especially females are attracted to cigar due to their flavour and
lesser cost when compared to cigarettes. They also think that cigar is less harmful than
conventional cigarettes due to the fact that they need not inhale the smoke from cigar. In
contrary, studies state that cigars are equally as harmful as cigarettes. In cigars the
concentration of nitrogen oxide, ammonia, carbon monoxide and tar are higher than in
cigarettes. It also contains nicotine in content equivalent to cigarettes, and are capable of
producing dependence of nicotine or addiction. Tobacco affects almost all organs of the
human body.(25, 50, 51)
Some of the systemic health effects of smoking tobacco are listed below:
a. Malignancy
b. Respiratory diseases
c. Cardiovascular diseases
d. Endocrine disorders
e. Gastrointestinal disorders
f. Reproductive disorders
g. Immunologic diseases
h. Neurologic diseases
i. Dermatological diseases
a. Malignancy:
Benowitz et al in 2010 stated that smoking is the largest preventable cause for cancer,
accounting approximately 30% of the deaths due to cancer. Tobacco smoking has been
proven to cause cancers of the lung, larynx, oral cavity, pharynx, oesophagus, pancreas,
bladder, kidney, cervix, stomach, colorectal and liver cancers, and acute myeloid
leukaemia.(25, 51)
The Tobacco Smoke (TS) contains more than seventy types of carcinogens (Leon et al.
2015; Established list 2012). Tobacco fumes are flooded with carcinogens namely 4 (Methyl
nitrosamino)-1-(3-pyridyl)-1-butanone (NNK), N-nitroso nornicotine (NNN), 1-
Hydroxypyrene, benzo(a)pyrene, 4-Nitroquinoline 1-oxide (4NQO) and nicotine (Hecht

51
2003). Tobacco and its smoke contain radioactive elements like 210Pb, 210Po, 226Ra, 228Ra
and 40K, capable of getting assimilated in cells of oral mucosa and organs like kidney,
respiratory tract and spleen (Savidou et al. 2006; Papastefanou 2009; Nagamatsu et al. 2011).
Conjointly, tobacco and its smoke contain heavy metal ions like iron, copper, and chromium,
nickel, lead, cadmium, mercury, arsenic, and antimony ions (Bagchi 1997). The heavy metal
ions catalyze the generation of reactive oxygen species which induce cellular damages in the
exposed tissue structures (Bagchi 1997).(51, 52)
➢ Carcinogens In Tobacco Smoke:
International Agency for Research on Cancer has listed the carcinogens, which are as follows
Table 5: Carcinogens in tobacco smoke
S.NO. Carcinogen Quantity (per cigarette)
Polycyclic aromatic hydrocarbons
1. Benz[a]anthracene 20–70 ng
2. Benzo[b]fluoranthene 4–22 ng
3. Benzo[j]fluoranthene 6–21 ng
4. Benzo[k]fluoranthene 6–12 ng
5. Benzo[a]pyrene 8.5–17.6 ng
6. Dibenz[a,h]anthracene 4 ng
7. Dibenzo[a,i]pyrene 1.7–3.2 ng
8. Dibenzo[a,e]pyrene Present
9. Indeno[1,2,3-cd]pyrene 4–20 ng
10. 5-methylchrysene ND–0.6 ng
Heterocyclic compounds
11. Furan 20–40 μg
12. Dibenz[a,h]acridine ND–0.1 ng
13. Dibenz[a,j]acridine ND–10 ng
14. Dibenzo[c,g]carbazole ND–0.7 ng
15. Benzo[b]furan Present
N-nitrosamines
16. N-nitrosodimethylamine 0.1–180 ng
17. N-nitrosoethylmethylamine ND–13 ng

52
18. N-nitrosodiethylamine ND–25 ng
19. N-nitrosopyrrolidine 1.5–110 ng
20. N-nitrosopiperidine ND–9 ng
21. N-nitrosodiethanolamine ND–36 ng
22. N’-nitrosonornicotine 154–196 ng
23. 4-(methylnitrosamino)-1-(3-pyridyl)
1-butanone
110–133 ng
Aromatic amines
24. 2-toluidine 30–200 ng
25. 2,6-dimethylaniline 4–50 ng
26. 2-naphthylamine 1–22 ng
27. 4-aminobiphenyl 2–5 ng
Heterocyclic aromatic amines
28. 2-amino-9H-pyrido[2,3-b]indole 25–260 ng
29. 2-amino-3-methyl-9H-pyrido[2,3-b]indole 2–37 ng
30. 2-amino-3-methylimidazo[4,5-f]quinoline 0.3 ng
31. 3-amino-1,4-dimethyl-5H-pyrido [4,3-b]indole 0.3–0.5 ng
32. 3-amino-1-methyl-5H-pyrido[4,3-b]indole 0.8–1.1 ng
33. 2-amino-6-methylpyrido[1,2-a:3′, 2′-d]imidazole 0.37–0.89 ng
34. 2-aminodipyrido[1,2-a:3′,2′-d]imidazole 0.25–0.88 ng
35. 2-amino-1-methyl-6-phenylimidazo [4,5-b]pyridine 11–23 ng
Aldehydes
36. Formaldehyde 10.3–25 μg
37. Acetaldehyde 770–864 μg
Phenolic compounds
38. Catechol 59–81 μg
39. Caffeic acid <3 μg
Volatile hydrocarbons
40. 1,3-butadiene 20–40 μg
41. Isoprene 450–1,000 μg
42. Benzene 12–50 μg
Nitrohydrocarbons

53
Some of the strongest of carcinogens such as Polycyclic Aromatic Hydrocarbons
(PAHs), N-nitrosamines, and aromatic amines, occurs in low amount, some of the weaker
carcinogens, such as acetaldehyde and isoprene, occur in the higher amounts. Hence a simple
addition of these of the carcinogenic agents can be misleading.(51)
PAHs are incomplete products of combustion which was first identified as
constituents of coal tar (Phillips 1983). This product occur as a mixture in tar, grilled foods,
soot, automobile engine exhaust, and others that are generated by incomplete combustion
(IARC 1983). Generally, they are carcinogens which act locally. Some of them like
benzo[a]pyrene (B[a]P) – a PAH, constitute a powerful carcinogenic activity.(51)
43. Nitromethane 0.5–0.6 μg
44. 2-nitropropane 0.7–1.2 ng
45. Nitrobenzene 25 μg
Miscellaneous organic compounds
46. Acetamide 38–56 μg
47. Acrylamide Present
48. Acrylonitrile 3–15 μg
49. Vinyl chloride 11–15 ng
50. 1,1-dimethylhydrazine Present
51. Ethylene oxide 7 μg
52. Propylene oxide 0–100 ng
53. Urethane 20–38 ng
Metals and inorganic compounds
54. Arsenic 40–120 ng
55. Beryllium 0.5 ng
56. Nickel ND–600 ng
57. Chromium (hexavalent) 4–70 ng
58. Cadmium 41–62 ng
59. Cobalt 0.13–0.20 ng
60. Lead (inorganic) 34–85 ng
61. Hydrazine 24–43 ng
62. Radioisotope polonium-210 0.03–1.0 picocurie

54
N-nitrosamines are a larger class of carcinogens whose activity is demonstrated in at
least 30 animal species (Preussmann and Stewart 1984). They act as systemic carcinogens
that affect different tissues depending on the structure involved. The most common N-
nitrosamines are N’-nitrosonornicotine (NNN) and the tobacco-specific 4-
(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) (Hecht and Hoffmann 1988) because
most of the commercial tobacco products contain these together, whose formation occurs
mainly during the curing step of tobacco production. High concentration of NNN and NNK
can be due to the midrib (central vein of the leaves) of Burley air-cured tobacco or the leaf
blade of flue-cured tobacco, or due to the retention of tobacco leaves under humid conditions
or in bales (cubes of tobacco tied together). These processes can encourage bacterial growth,
leading to increased nitrite content, and heating with propane during curing. Indirect fire
methods were used instead of direct-fire, and the levels of NNK and NNN in cigarette
tobacco were examined. Reduction of about 65–78% of NNN and 60–85% in NNK levels
were observed (Rickert et al., 2008).(51, 52)
Yuan et al in 2009 conducted studies on the relationship of NNK with lung cancer in
smokers and stated that metabolites of NNK have a significant association with the risk of
developing lung cancer in a dose-dependent manner. NNK has consistently caused tumours
in mice, rats, hamsters and tumour of nasal cavity in rats and mink. NNN has caused tumours
of the oesophagus in rats, and nasal cavity in multiple species. NNN and NNK in
combination can cause tumours of oral cavity in rats and nasal cavity in mink.(52)
Aromatic amines in the smoke are products of combustion which includes 2-
naphthylamine and 4- aminobiphenyl (4-ABP), and were characterized as human carcinogens
based on exposures related to the dye industry (Luch 2005). Heterocyclic aromatic amines are
again combustion products which are known for their occurrence in grilled foods (Sugimura
1995), but is also seen in cigarette smoke.(51)
Other carcinogenic compounds in the cigarette smoke includes the human carcinogens
Vinyl Chloride (VC) in lesser amounts and ethylene oxide in limited quantities (IARC
1979).(51)
VC is seen more commonly in PVC industries, and is thought to be associated with
occupationally hazardous category. VC in the Tobacco Smoke of the cigarettes accounts
about 1.3-16 mg/cigarette and of small cigars 14 to 27 mg/ cigar. The filter cigarettes reduce
VC in Tobacco Smoke. Animal studies suggest VC to be a multisite carcinogen. In humans

55
VC is said to contribute to Haemangiosarcoma of liver, malignancy of brain, lung, lymphatic
and haematopoietic system. (53)
Ethylene oxide is linked with malignancies of the hematopoietic and lymphatic systems
(IARC 1994). (51)
Nickel has been shown to cause a number of different forms of cancer, especially of the
respiratory tract. The main mechanism responsible for this activity is that Ni is mutagenic and
has been reported to induce sister chromatid exchanges.(74)
➢ Events Related to Tobacco Smoking in Carcinogenesis:
Cancer susceptibility is determined by the metabolic activation and detoxification
process. Most cigarette smoke carcinogens require a metabolic activation process,
generally catalysed by detoxifying enzymes, to convert them to electrophilic entities that
can covalently bind to DNA, forming DNA adducts. (55)
But some of the detoxifying
enzymes help in elimination of the carcinogen from the body. The balance between
carcinogen metabolic activation and detoxification varies among individuals and is likely
to affect cancer susceptibility. Person with higher metabolic activation and lower
detoxification rate are at a higher risk from smoking-related cancers. (51, 54, 55)
Action of Detoxifying Enzymes:
A number of enzyme families are important in both the activation and detoxification of
carcinogens in cigarette smoke. Some of them are:
▪ Cytochrome P-450s
▪ Glutathione-S-Transferases (GSTs)
▪ Uridine-5′-Diphosphate-Glucuronosyltransferases (UGTs)
▪ N-acetyl-transferases (NATs)
▪ Epoxide hydrolases
▪ Sulfotransferases
▪ Cytochrome P-450s are encoded by CYP genes. They are microsomal enzymes that
catalyse the oxidation of myriad chemicals, including many of the carcinogens in
cigarette smoke. Shimada et al in 2004 stated that the Polycyclic Aromatic
Hydrocarbons (PAHs) are metabolized by P-450 1A1, 1B1 by interaction with the aryl
hydrocarbon receptor. (51, 54)
Kim and Guengerich in 2005 stated that aromatic amines

56
are metabolized by P-450 1A2 and Yoo et al in 1988 stated that N nitrosamines are
metabolised by P-450s 2A6, 2A13, and 2E1.(51)
These enzymes convert the carcinogen
to forms which can covalently bind to DNA and form DNA adducts. (51, 54)
▪ Glutathione-S-Transferases (GSTs) are the one of the enzymes that detoxify the
epoxides in conjugation with glutathione. The reaction is catalysed by cytosolic GSTs.
The members of GST class include GSTA1-1, GSTM1-1, GSTP1-1, and GSTT1-1.
Hayes et al in 2005 stated that polymorphisms in genes that encode these subunits are
found especially in smokers with cancer risk. Jernstrom et al in 1996 stated that
GSTA1-1, GSTM1-1, and GSTP1-1 catalyse glutathione conjugation of PAHs. Norppa
et al. 1995 stated that GSTM1-1 and GSTT1-1 play an important role in conjugation of
two 1,3-butadiene epoxide metabolites. Brown et al. 1996 stated that Ethylene oxide is
also detoxified by the same.(51)
▪ Uridine-5′-Diphosphate-Glucuronosyltransferases (UGTs) are the enzymes that promote
a number of carcinogens in tobacco smoke to conjugate with glucuronic acid (Bock
1991, Nagar and Remmel 2006). The metabolites of PAHs (phenol and diol) are
eliminated as glucuronide conjugate (Bock 1991). Carmella et al in 2002 and Bock in
1991 stated that glucuronidation plays an important role in excretion of NNK
metabolites in smokers and also in benzene detoxification.(51)
Thus higher metabolic activation ends up with the formation of DNA adducts. (54, 55)
Formation of DNA Adducts:
DNA bases may serve as reactive side branches which can covalently associate with
carcinogenic components and form unnatural DNA structures called as DNA adducts. (54)
Numerous studies have evaluated DNA adduct formation in foetuses and in various tissues
and fluids of smokers, including samples from the larynx, oral and nasal mucosa, bladder,
cervix, breast, pancreas, stomach, placenta, and cardiovascular system, and samples of
sputum, sperm, and blood cells. (55)
Some carcinogens does not undergo metabolic activation to form adducts, they
directly enter this step. Higher the formation of DNA adducts more are the chances of
developing cancer. Continuous formation of DNA adducts can cause miscoding during
replication of DNA when DNA polymerase enzymes process these adducts incorrectly. Thus
gene mutations have the ability to cause loss of normal functions in controlling of cellular
growth via a complex signal transduction pathway ultimately resulting in genomic instability,

57
cellular proliferation and cancer. The protective apoptosis can counterbalance these mutations
by removing the cells whose DNA are damaged. Thus, the mechanisms that lead to apoptosis
and those mechanisms that suppress the apoptosis also have a major impact on tumor growth.
(55)
The following is the pathway for cancer causation in cigarette smoking:
Figure 28 : Pathway of cancer causation in cigarette smoking
Evidence of DNA Adducts - Micronuclei:
The exfoliated buccal cells of the smokers show a higher number of micronuclei, the
extra-nuclear structures, located in cytosol. They are formed during the metaphase to

58
anaphase transition of the basal cells during cell cycle. The presence of micronuclei is
indicative of daughter cells with genomic complement deficiency.
Micronuclei may contain mis-segregated chromosomes or broken fragments of
chromosome (Bhat et al. 2015). Sabharwal et al in 2015 stated that micronuclei formation
acts as a biomarker for abnormalities of nucleus and chromosome that is induced in oral
epithelium by the genotoxins. The TS induces DNA breakages, and cancer cells are more
susceptible to the DNA damages than the healthy cells.(55, 56)
Processes of Counterbalancing Mutation:
Inside every cell, the effects of mutation resulting from DNA adduct formation can be
counterbalanced by two processes:
1. Apoptosis
2. Cellular Repair System
3. Cellular Senescence
Apoptosis:
Apoptosis, or programmed cell death is a protective process that removes the cells
with DNA damage and thereby, counterbalances the mutational events. Martin in 2002 stated
that apoptosis is a critical event for eliminating injured unstable cells thereby minimizing
damage to the surrounding normal cells. Rich et al in 2000 stated that induction of apoptotic
process prevent the growth of cancer cells. The balance between the mechanisms leading to
apoptosis and suppressing apoptosis has a major impact on cancer progression. (56)
Cellular Repair System:
The Cellular repair system has the ability to remove DNA adducts and turn the
structure of the malformed DNA to a normal one. When these repair enzymes are overloaded
by DNA damage, they cannot function efficiently resulting in persistence of DNA adducts
which can lead to a higher chance of developing cancer. (57)
The cellular repair enzymes include:
▪ DNA polymerase
▪ DNA ligase

59
The DNA polymerase is the enzyme which synthesizes DNA by fixing the nucleotides
together. The DNA ligase is the enzyme that is involved in joining the ends of the strands of
the DNA together by covalent bond to make a continuous DNA strand. The sequential action
of both these enzymes is required for formation of normal DNA. (57)
Cellular Senescence:
Cellular aging is associated with replicative senescence of the cells as a result of progressive
decline in life span and function of the cells. After a limited number of divisions, the normal
cells become arrested in a terminally non dividing state, known as replicative senescence. In
human cells, the replicative senescence involves progressive shortening of the telomeres that
ultimately results in arrest of cell cycle. The Telomeres are short repeated sequences of DNA,
which are present at the end of chromosomes, ensuring the complete replication of
chromosomes and protecting them from fusion and degradation. When the somatic cells
replicate, a smaller section of telomere is not duplicated and becomes progressively
shortened. As they become shorter, the ends of chromosomes cannot be protected and are
seen as DNA breakage, which signals arrest of cell cycle.
It has been postulated that free radicals also has a role in DNA damage that leads to aging but
remains controversial. Metabolic insults that get accumulated over a period of time may
cause damage to the nuclear and mitochondrial DNA. Though most of the DNA damages are
repaired by DNA repair enzymes, some of them persists and accumulates as the cells age and
this normally results in cellular senescence. When the mechanism of Cellular senescence is
breached, the damaged DNA enters into cell cycle which can lead to a chance of developing
cancer.
The following are the list of carcinogens involved in certain cancers:
Table 6: Carcinogens in certain type of cancer
S.No. Type of
Cancer
Carcinogen Involved
1. Lung Polycyclic Aromatic Hydrocarbons, N-nitrosamines 4-
(methylnitrosamino)-1-(3-pyridyl)-1-butanone, ethyl carbamate,
isoprene, ethylene oxide, benzene, aldehydes
2. Larynx Polycyclic Aromatic Hydrocarbons
3. Oral cavity Polycyclic Aromatic Hydrocarbons, N-nitrosamines 4-

60
(methylnitrosamino)-1-(3-pyridyl)-1-butanone, N-nitrosonornicotine
4. Esophagus N-nitrosonornicotine, other N-nitrosamines
5. Cervix Polycyclic Aromatic Hydrocarbons, N-nitrosamines 4-
(methylnitrosamino)-1-(3-pyridyl)-1-butanone
6. Liver N-nitrosamines 4- (methylnitrosamino)-1-(3-pyridyl)-1-butanone,
other N-nitrosamines
7. Pancreas N-nitrosamines 4- (methylnitrosamino)-1-(3-pyridyl)-1-butanone
8. Leukemia Benzene
➢ Malignancy of Respiratory Tract
▪ Lung Cancer:
Lung cancer is the dominant malignancy caused by smoking. According to WHO (2019),
the total number of cases is estimated to be 1.2 million annually, with about 90% attributed to
smoking.(25)
There is increase in risk of all histologic types of lung cancer: squamous cell
carcinoma, small cell carcinoma, adenocarcinoma (including bronchiolar– alveolar
carcinoma) and large cell carcinoma.(55)
The strongest determinant of lung cancer in smokers is duration of smoking, the risk also
increases with the number of cigarettes smoked. Smokers are up to 22 times more likely to
develop lung cancer in their lifetime than non-smokers. Cigarette smoking is the most
strongly active risk factor in female lung cancer.(57, 58)
Cigar and/or pipe smoking are also causally associated with lung cancer. Mayer stated
that the risk of developing lung cancer in cigar smokers is 5 times higher than non-smokers.
Those who smoke ﬁve or more cigars per day have the risk of dying from lung cancer 23
times more when compared with a non-smoker. (58, 59)
Lung cancer rates have been shown to
be inversely related to vitamin A intake. Pastorino et al. have previously shown that vitamin
A protects against lung cancers related to tobacco smoking.(57, 58)
▪ Laryngeal Cancer:
Laryngeal cancer is caused by cigarette smoking, and the risk increases with duration of
smoking and number of cigarettes smoked. Risk is greatly enhanced by alcohol consumption
and decreases upon cessation. National Cancer Institute states that there is a six fold increase
in risk for developing laryngeal cancer for those who smoke one or more cigars per day than

61
a non-smoker.(55, 57 - 59)
Cigar smokers have a 4–10 times greater risk of dying from
laryngeal, oral, and oesophageal cancers as compared with non-smokers. (58)
Cigarette smoking also increases the risk of nasal, sinonasal and nasopharyngeal
cancer.(25, 51, 55)
➢ Malignancy Of Gastrointestinal Tract:
▪ Oral Cancer:
When a person is smoking, the oral cavity is continuously in contact with the tobacco
fumes.(54)
Based on numerous studies, cigarette smokers have risks of oral cancer two to five
times than that of non-smokers. The risks increase with the numbers of cigarettes smoked(53)
and years smoked and the risk decreases with smoking cessation.(57)
Heavy smokers who
drink alcohol heavily have many times the risk of oral cancer as that expected from the
independent effects of smoking and alcohol intake.(53, 57)
Cigar smokers are seven to ten times
more likely to develop oral cancer than non-smokers.(58)
The pH of cigar smoke is more than
cigarettes making the nicotine content absorbed readily by the oral mucosa. As cigar smoke is
not inhaled mostly by the smokers, the nicotine content does not enter the lung directly;
instead it is absorbed in the oral mucosa. The saliva also contains nicotine content which
when swallowed causes cancer in the oral mucosa and oesophagus. (55)
Garrote et al stated that
cigar smokers are equally prone to oral cancer as cigarette smoker. (59)
In some studies it was
shown that 10 years after quitting, former smokers have the same risk of oral cancer as
people who never smoked, whereas other studies show that the risk decreases dramatically
but remains at a level somewhat higher than that found in people who never smoked. (25)
The
pipe smokers had a 2.0 to 3.5-fold increased risk of developing oral cancer compared to
persons who did not smoke.(25)
75 to 90% of all oral cancer cases are explained by the combined effect of smoking and
alcohol use. (54, 60)
Smoking when combined with alcohol consumption of more than 80g, or
more than five to six drinks per day is said to increase the risk of developing cancers (Pöschl
and Seitz 2004).(60, 61, 62)
Although several mechanisms were proposed suggesting the role of
alcohol in oral carcinogenesis, the exact mechanism is not well understood. This could be
because alcohol dissolves certain carcinogenic compounds in tobacco smoke and also
increases the permeability of the oral epithelium.(54, 60)
Ethanol in the alcoholic beverages is
metabolized into acetaldehyde, a known carcinogen. In addition, PAHs and nitrosamines

62
(carcinogens) may be present in some of alcoholic beverages. Nutritional deficiencies along
with heavy consumption of alcohol may contribute to carcinogenesis. (62)
▪ Pharyngeal Cancer:
Cigarette smoking is a cause of oropharyngeal and hypopharyngeal cancer and the risk
increases with duration of smoking and daily cigarette consumption and decreases with time
since quitting.(51, 55)
▪ Oesophageal Cancer:
Cigarette smoking causes cancer of the oesophagus, particularly squamous cell cancer. It
is also a cause of adenocarcinoma of the oesophagus, which has been increasing. The risk for
oesophageal cancer is related to duration of smoking and number of cigarettes smoked per
day and remains elevated after cessation. Cigar smokers have two fold increased mortality
rate for oesophageal cancer than non-smokers states a study. Another study by Shapiro et al
2000, reported a 4 to 5 fold increase in mortality rate from oesophageal cancer.(51, 58)
➢ Breast And Cervical Cancer:
Studies have demonstrated a link between tobacco smoking and an increased risk of breast
cancer, particularly among heavy smokers and women who start smoking before their first
pregnancy. Smoking also increases the risk of cervical cancer (Squamous cell Carcinoma) in
women infected with Human Papilloma virus. The risk of these cancers typically increases
with intensity and duration of smoking, because of the continued exposure to toxins and
carcinogens. (25)
➢ Malignancy of Renal System:
Cancer of the kidney and of the lower urinary tract that includes the bladder, ureter and renal
pelvis are also associated with smoking. (25)
Pitard et al stated that cigar smoking has risk for
developing bladder cancer than cigarette smokers. (58)
➢ Others:
Cigarette smoking is a cause of developing liver cancer, independent of the effects of
hepatitis B and C infection and alcohol consumption.(57)
Another study stated that cigar
smoking is associated with pancreatic cancer. Smokers are also at a significantly higher risk
of developing acute myeloid leukaemia. (51)

63
Respiratory Diseases:
According to World Health Organization in 2019, about 40% of all the tobacco related
deaths are due to lung diseases like chronic respiratory diseases, cancer and tuberculosis.
Every year about at least 8 million people are killed by tobacco due to respiratory diseases.
(25, 63)
➢ Chronic Obstructive Pulmonary Disease(COPD):
According to WHO, one in five tobacco smokers will develop (COPD) in their lifetime,
especially people who start smoking during their childhood as TS significantly slow lung
growth and development. Smokers are 3–4 times at a higher risk for developing COPD than
non-smokers. (25)
Cigar smokers also have a direct relationship with COPD. They have higher
mortality rate than non-smokers, and are 1.336 times at risk to die from COPD than non-
smokers. (59, 64, 65)
In COPD, Tobacco smoking causes rupturing of the air sacs in the lungs, thereby reduces
the capacity of lungs to take in oxygen and expel carbon dioxide. It can also cause
accumulation of purulent mucus, resulting in a painful cough and severe breathing
difficulties. (25)
Some studies state that smoking causes decrease in the level of lung surfactant
phosphatidylcholine but others reported no difference in lung lavage phospholipid
concentration between smokers and non-smokers. But many studies also stated that smoking
decreases the surfactant activity of bronchoalveolar lavage fluid. Thus the findings indicate
the variable effects of cigarette smoke on surfactant level and surfactant activity.(64, 65)
Adults who were exposed to second hand smoking as children and had frequent lower
respiratory infections as a result, are also at risk of developing COPD. (25)
Non-smokers
exposed to Environmental Tobacco Smoke (ETS) have changes in lung function. An
epidemiological study conducted in Europe comprising 7882 adults revealed that passive
smoking is associated with nocturnal breathlessness, nocturnal chest tightness, and
breathlessness after periods of activity, and increased bronchial responsiveness. The smoke
impairs the airway epithelial cells to support repair processes, and also contribute to
alterations in airway structures. Although cigarette smoking is strongly associated with the
development of COPD, the effects of exposure to ETS on COPD are controversial. (59, 64, 65)

64
➢ Asthma:
Asthma is one among the common respiratory diseases. It is a chronic inflammatory
disease of the airway, which can be due to hyper responsiveness to specific triggers that can
lead to wheezing, chest tightness, and dyspnoea. (66)
Smoking exacerbates asthma in adults, requiring emergency health care.(25)
Active
smoking appears to be an important risk factor for asthma. It plays detrimental effects on the
airway epithelium and smooth muscles causing changes in lung function. It may worsen
outcomes with regard to both morbidity and mortality due to asthma.
There is a causal relationship between parental smoking and the development of asthma
in children. Larsson ML et al in 2001 conducted a study in Sweden to examine if exposure to
Environmental Tobacco Smoke (ETS) during childhood has impact over asthma prevalence
in adults, and to identify the problems from ETS. He concluded that Childhood exposure to
ETS was related to an increased prevalence of asthma among adult non-smokers, and some
are also more likely to become smokers. ETS was also found to be a major irritant of lower
airway. In a 15-year follow-up of African–American women the incidence of onset of asthma
was increased by, 40% among smokers and 20% among passive smokers when compared
with women of no tobacco exposure. A systematic review and meta-analysis conducted by
Silvestri M et al concluded that maternal smoking during prenatal period aids in induction of
asthma and wheezing in the offspring, especially in the first years of life. (66, 67)
➢ Tuberculosis (TB):
More than 20% of global incidence of TB is due to smoking. Smoking is a greater risk
factor for TB, independent of socioeconomic status and alcohol consumption.
Tuberculosis is an infectious bacterial disease that damages the lungs and decreases the
lung function. (25, 68)
It itself can lead to chronic respiratory disease, especially bronchiectasis
and COPD. Smoking increases the susceptibility to develop TB by altered immune response
and mechanical disruption of cilia function. (68, 69, 70)
According to WHO, active TB cases along with tobacco smoking substantially increases
the risk of disability and death from respiratory failure. (68, 69, 70)
About one quarter of the
entire world’s population possesses latent tuberculosis, thereby increasing the risk of
developing active disease. Smoking not only doubles the risk of latent tuberculosis state to an

65
active state, it also worsens the progression of the disease. Smokers are twice likely to fall ill
with TB. (25, 68)
➢ Other Respiratory Illnesses And Reduced Lung Function:
Tobacco smoking has the ability to cause pneumonia and all major respiratory symptoms,
like coughing, phlegm and wheezing. Lung function and growth are more likely to be
compromised among smokers. The children of smoking parents suffer similar respiratory
symptoms and lower levels of lung function in their entire childhood. (25)
b. Cardiovascular Diseases (CVD)
Cardiovascular diseases are the most common diseases elicited due to tobacco smoking,
followed by respiratory and other system involvement (Action on Smoking and Health,
2016). According to WHO 2019, tobacco use and second hand smoking are the major
contributors, causing about 3 million cardiovascular deaths globally every year.(25)
Another
WHO report from India, 2018 stated that, 48% of the total tobacco death is due to
cardiovascular diseases. CVDs are more likely to occur in younger individuals from 30 to 44
years of age. 16% of the total CVDs are caused by tobacco smoking. (71)
Smokers have up to
twice the risk of stroke and a fourfold increased risk of heart disease. Those who smoke just
one cigarette per day are already half as likely as those who smoke 20 per day to develop
heart disease and stroke. (25)
It is said that the free radicals generated by smoke are inhaled, hence there is an increased
levels of reactive oxygen species derivatives generated in the lung of the smokers by
phagocytes. These reactive oxygen species derivatives could in turn enter into the circulation
and thereby cause cardiovascular problems (71, 72)
Chemicals in the TS that is inhaled causes the cells that line the blood vessels to become
swollen and inflamed. This can narrow the vessel walls and can lead to many cardiovascular
conditions which includes the following manifestations – endothelial dysfunction,
inflammation, altered lipid metabolism, increased demand for myocardial oxygen, insulin
resistance.
The constituents of TS that has received greatest attention as potential factors that can
contribute to CVD are nicotine, carbon monoxide (CO), and oxidant gas. Some researchers
also state that PAHs, and other particulate matters of the TS are involved in the
pathophysiology of CVD(Brook et al in 2004; Bhatnagar 2006).(72)

66
Nicotine is a sympathomimetic drug which releases catecholamines systemically from the
adrenal gland and locally from the neurons. Pharmacodynamic studies of nicotine indicate
that though tolerance to effect of nicotine develops rapidly, the tolerance is incomplete
(Porchet et al in 1987). Benowitz et al in 1982 conducted a study with constant intravenous
infusion of nicotine and found that the nicotine increased the heart rate even when their level
in the blood was relatively low, and as the infusion continued, the Heart Rate (HR) reached a
plateau in spite of a progressive rise in blood levels of the nicotine. This same phenomenon
was observed in HR with level of blood nicotine during cigarette smoking throughout the day
(Benowitz et al in 1984).(72)
CO is another major constituent of TS. The CO binds readily to the haemoglobin, thereby
reducing the haemoglobin content available to carry oxygen and impeding release of oxygen
by haemoglobin. Studies conducted by Calverley et al in 1981 and by Allred et al in 1989
stated that inhalation of CO in smokers decreased exercise tolerance in patients with angina
pectoris and intermittent claudication. De Bias et al in 1976 stated that inhalation of CO
reduces the threshold for ventricular fibrillation in animals. Benowitz in 2003 stated that long
term exposure to CO in smokers resulted in increased red blood cell mass and decreased
oxygen carrying capacity of the red blood cells, resulting in hypoxemia. In response to
hypoxemia, the red blood cell masses increase in order to maintain the amount of oxygen
required by the organs in the body. The increase in red blood cell mass further increases the
blood viscosity and can contribute to hypercoagulation in the smokers. (72, 73)
TS contribute a greater level of oxidizing chemicals to smokers, which includes oxides of
nitrogen and free radicals (Church et al 1985). Exposure to oxidant chemicals in theTS is
associated with the depletion of antioxidants, which is manifested as reduced levels of
vitamin C in the blood of the smokers than in non-smokers (Lykkesfeldt et al in 2000).
Smoking was also reported to increase lipid peroxidation product levels in the plasma and
urine of the smokers (Morrow et al in 1995). Studies also indicate that oxidant stress
contributes to many potential mechanisms including inflammation, endothelial dysfunction,
lipid abnormalities, and platelet activation (Burke and FitzGerald 2003).(71)
Endothelial dysfunction:
Nicotine, free radicals in smoke, oxidants from the TS, free radicals produced by the
endothelial cells themselves in response to TS, decrease the availability of nitric oxide.
Hence, there is no response to stress or vasoconstriction is encountered (U.S. Department of

67
Health and Human Services 2014; Barua et al 2001; Ichiki et al 1996). Vasoconstriction, in
turn, increases the prothrombotic response. TS induced damage to endothelium alters the
interaction with flowing blood cells, thereby causing the inflammatory substances and
platelets to stick to the vessel wall.
This further decreases the ability of endothelium to regulate local levels of clot formation
and clot dissolving substances (U.S. Department of Health and Human Services 2014; Nowak
et al 1987). Smoking reduces elasticity of the arteries, which results in stiffening of the walls
and thereby reducing the coronary flow reserve (Celermajeret al 1993; Stefanadiset al 1997).
(73)
Bernhard et al in 2005 stated that TS contains a number of metals, including
▪ Aluminium
▪ Cadmium
▪ Copper
▪ Lead
▪ Nickel
▪ Mercury
▪ Zinc
These metals catalyse oxidation reaction of the cellular proteins. This reaction may lead to
cellular damage structurally and also endothelial dysfunction and separation of endothelial
cells from the vessel walls. Mixture of both the metals and oxidant may be involved in
damaging the endothelial cells. (72, 73)
The effects of smoking on endothelium occurs early, studies suggest that exposure of about
one hour or less to TS, results in endothelial damage which can be long lasting (Juonala et al
2012). Cessation of smoking is associated with improved endothelial function (Johnson et al
2010).
➢ Metal Contents In Cigarette:
▪ Aluminium:
Aluminium is greatly concentrated in the cigarettes, whose values ranging from 699–
1200mg/g. It also has role in the development of microcytic anaemia and osteomalacia and
has the potential for inﬂammatory and oxidative events.(74)

68
▪ Cadmium:
The main source of cadmium (Cd) in humans is through cigarette, the average Cd content
per cigarette is between 0.5 and 1.5mg. When smoking of the cigarette is done, the Cd is
transformed into cadmium oxide, which is then inhaled by the person. Satarug et al reported
that smokers have a 1.7 fold increase of serum Cd content compared to non-smoker. Mortada
et al. reported that the mean blood Cd content in the smokers was 1.9 times higher than non-
smokers. Barany et al. found that the serum Cd values of smokers were at least 3.1 fold
higher in comparison to non-smokers. Cadmium levels are higher in serum of smokers, and
cadmium accumulates in the aortic walls of smokers (Abu-Hayyeh et al.
2001).(74)
Epidemiologic evidence indicates an association between serum levels of cadmium
and lead and CVD, including hypertension and MI (AbuHayyeh et al. 2001). (73)
▪ Copper:
The Cu content in the tobacco leaves was said to be 156 mg/g. Serum concentrations in
the smokers who smoke for more than 10 cigarettes per day accounts 0.95 mg/l in youngsters,
1.10 mg/l and 1.31 mg/l in adults. Lapenna et al in 1995 suggested correlation between Cu
levels in plasma and lipid peroxidation in the smokers.(74)
▪ Lead:
The Pb content per cigarette is around 1.2mg, about 6% of the content passes to the
mainstream smoke, which is inhaled by the smokers. Blood brain barrier is quite
impermeable for Pb, hence children are especially at high risk to accumulate Pb in the brain
and central nervous system, which can result in mental retardation. Other health
consequences associated with accumulation of lead are peripheral arterial diseases and
hypertension. (74)
▪ Nickel:
Evidence suggest that Ni affects development of heart in unborn mice. Ni content in the
tobacco plant accounts for about 0.64 and 1.15 mg/g, and varies in cigarettes from 0.078 mg
to 5 mg. Serum levels of Ni were analysed, and said that smoking is not an important source
for Ni.(74)
➢ Coronary Heart Disease:

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