Carcinogenesis is the process by which genetic damage leads to neoplastic transformation in cells, involving carcinogens such as chemical agents, radiation, and oncogenic viruses. The process includes initiation, which is a permanent DNA change, and promotion, which is reversible and does not induce tumors by itself. Various chemical, radiation, and viral factors contribute to different types of cancers, and key genes like oncogenes and tumor suppressor genes play crucial roles in tumor development.

1. Carcinogenesis

2.  Carcinogenesis :
 is the process of genetic damage and induction of
neoplastic transformation of cells.
 Carcinogens:
 are agents by which neoplastic transformation of
cells occur.

3.  Carcinogens include the following:
1. Chemical carcinogens.
2. Radiation energy.
3. Oncogenic viruses and some other microbes.
 Each group of agents is considered separately, but
several may synergize the effects of others.

4.  Chemical carcinogenesis:
 It is multi-step process.
 Requires initiation and promotion.
 Initiation is irreversible permanent change in DNA
of target cells and rapid; results from exposure to a
carcinogen .
 Promotion is reversible, must follow initiation.
 Promotion can not induce tumour by itself.

5.  Some chemical carcinogens :
1. Can both initiate and promote (complete).
2. Others only initiate (incomplete).
 Chemical carcinogen can act either:
1. Directly which are highly reactive.
2. Indirectly need to be modified (procarcinogens).

6.  Promoters include:
1. Phorbol esters .
2. Phenols.
3. Hormones.
4. Drugs.
 Promoters are not electrophilic and do not damage
DNA.

7.  Carcinogenic chemicals:
 Alkylating agents: weak carcinogens, induce
lymphoid neoplasms, example cyclophosphamide and
other anticancer drug.
 Polycyclic Aromatic Hydrocarbons: produced by
combustion of tobacco, most potent carcinogen
known, induce a wide variety of neoplasms.
 Aromatic Amines and Azo Dyes(food dyes): require
activation, cause hepatoceullar carcinoma and bladder
cancer.

8.  Naturally occurring carcinogens: aflatoxin from
Aspergillus flavus, potent hepatic carcinogen.
 Nitrosamines: require activation.
 Others: asbestos(bronchogenic carcinoma);
arsenic(skin cancer);nickel(lung cancer).

9.  Radiation carcinogenesis:
 Ultraviolet radiation:
• Causes squamous cell carcinoma, basal cell
carcinoma, and melanoma in sun exposed areas.
• Mechanism is due to formation of pyrimidine
dimers in DNA.
• Individuals with Xeroderma Pigmentosum have
increased risk(defect in DNA repair pathways).

10. Ionizing radiation:
 Electromagnetic radiation(x-rays, gamma rays).
 Particulate radiation(alpha,beta particles,neutrons).
 Both cause cancer.
 Dose, dose rate, and radiation quality and host repair
pathways all affect efficiency.
 Leukaemia is most common radiation induced
malignancy.
 Thyroid Ca,breastCa,and lung Ca.
 Skin,bone, and GI tract are more resistant.

11. Viral oncogenesis:
• DNA Viruses:
 Infection of a permissive cell results in full virus life
cycle and cell death.
 Transformation occurs following integration in non-
permissive cells in which expression of early genes is
still possible.
 Mechanisms of oncogenesis are diverse.

12.  Examples of DNA oncogenic viruses:
• Human Papilloma Virus(HPV):2,4,7 cause benign
papilloma of skin (wart).
• Human Papilloma Virus(HPV):6,11cause anogenital
and laryngeal papillomas and genital verrucous
carcinoma.
• 16,18,33 cause cervical and oral carcinoma.

13.  Hepatitis B Virus: 200fold increased risk of
hepatocellular carcinoma.
 Epstein-Barr Virus(EBV): associated with endemic
form of Burrkitt lymphoma, found in all cases of
nasopharyngeal carcinoma.

14.  RNA Viruses:
• All are retroviruses.
• Have three groups of genes:
I. Gag(core proteins).
II. Env(envelope proteins).
III. Pol(reverse transcriptase).

15.  Acute transforming Viruses:
• Contain a viral oncogene.
• Rapid induction of tumour.
• They are deficient –need helper.

16.  Slow transforming Viruses:
• All are replication competent.
• Contain no oncogenes.
• Tumorigenecity requires integration near proto-
oncogene.
• Proto-oncogenes activated by increased expression
or induction of a mutation.

17.  Human T-Cell Leukaemia Virus:
• Only known human RNA Virus.
• Binds to CD4 on T-Cells.
• HTLV-1:associated with adult T-Cell leukaemia.
• HTLV-2:associated with Hairy cell leukaemia.

18.  Oncogenes:
• Due to conversion of cellular proto-oncogenes.
• Produce onco-proteins that are involved in tumour
development .
• Onco-proteins have the ability to promote cell
growth in the absences of normal mitogenic signals.

19.  Onco-proteins act as:
1. Growth factors.
2. Growth factors receptors.
3. Cell cycle regulators.
4. Nuclear regulatory proteins.
5. Proteins involved in signal transduction.

20.  Tumour suppressor genes:
• The proteins that apply brakes to cell proliferation
are the products of tumour suppressor genes.
• Loss of function of these genes is a key event in
many human tumours.
• Example mutation in p53 is found in many tumours .
• P53gene is normal cell cycle arrest and apoptosis in
response to DNA damage.