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By
Dr. G. V. Mali
Department of Microbiology
Bharati Vidyapeeth’s
Matoshri Bayabai Shripatrao Kadam Kanya Mahavidyalaya,
Kadegaon Dist. Sangli
8th September 2018
Oncogenesis :
 Also termed as ‘Carcinogenesis’ – The process of
formation of Cancer
 Cancer- Latin Word – Meaning is Crab.
 Greek Physician Hippocrates – Crab like Disease.
 Definition – Abnormal , unregulated and uncontrolled
growth of cells – result is lumps or mass of cells
 Cancer is also known by the term – Tumor or
Malignancy
 Tumor is Latin word- means swelling
 Suffix ‘-oma’ is used to describe the Tumor
Types of Cancer :
Classification is done on two Criteria
1. Pattern of Growth
i. Benign Tumor ii. Malignant Tumor
2. Types of tissues in which it originates
i. Carcinomas ii. Sarcomas iii. Leukemias iv. Lymphomas
i. Benign Tumors -
• Cancer cells do not invade surrounding tissues
• Remain localized as a compact mass
• Encapsulated by a membrane called lamina
• Grow by displacing surrounding tissues
• They are not fatal, however…..
• They are usually removed by surgery
ii. Malignant Tumors -
• Cancer cells invade surrounding tissues, organs & other parts
• Capable of invasion and metastasis
• Not encapsulated by any membrane
• Growth is fast and lethal
• Resistant to treatment and may cause death
i. Carcinomas-
• Cancer of epithelial cells , most common
• Accounts for 85 – 90 % of total human cancers
• Skin, prostate , bladder , breast , linings of respiratory,
gastrointestinal , urinary and genital systems
•Two major subtypes-
•Adenocarcinoama-develops in organs and glands
•Squamous cell carcinoma- in sqamous epithelium
ii. Sarcoma -
• Cancer of supportive and connective tissues
• Bones, cartilages, muscles, blood vessels & tissues at joints
• Account for 1 % of total human cancers
• Arms , legs, hands , feet , chest , back , hips , shoulder,
abdomen, head and neck
iii. Leukemias- ( Blood cancer / liquid cancer )
• Cancer of blood forming cells (hematopoietic cells) of bone
marrow
• Accounts for 4% of total human cancers
• Hematopoietic cells produce WBCs
• Characterized by overproduction of abnormal & immature WBCs
• Such cells do not play role in the defense mechanism of body
• Four Types-
i. Acute lymphocytic leukemia(ALL)-Cancer of lymphocytes
ii.Acute myelogenous leukemia ( AML)- Cancer of granulocytes &
monocytes
•Chronic lymphocytic leukemia ( CLL)
•Chronic myelogenous leukemia ( AML)
iv. Lymphomas -
• Cancer of lymphatic tissues-lymphocyes, lymph nodes, lymph
vessels and lymphoid organs
• Accounts for 5% of total human cancers
•Two Types-
1. Hodgkin’s Lymphoma – Large, Binuclated cells called Reed-
Sternberg cells
2. Non Hodgkin’s Lymphoma – Do not contain Reed-
Sternberg cells
•Increased production of lytic
enzymes
•Genetic alterations
•Induction of neoplasm in
experimental animals
•Altered signal transduction
mechanism
•Alterations in electric charge
•Ability to host’s anti-tumor
immune response
•Alteration in cell membrane
structure and functions
Characteristics of Cancer Cells
•Infinite growth (Immortality)
•Metastasis
•Invasiveness
•Loss of contact inhibition
•Loss of anchorage
dependence
•Reduced serum requirements
•Growth factor independence
•Loss of cell differentiation
•Inhibition of apoptosis
•Angiogenesis
•Changes in cytoskeleton
•Changes in cell morphology
and cytology
HYPOTHESIS ABOUT CANCER
1. Somatic Mutation Hypothesis
i. Mutational activation of repressed genes
ii. Mutational blocking of repressed proteins that keep gene in
repressed condition
iii. Chromosomal abnormalities and cancer go hand in hand
2. Defective Immunity Hypothesis
• Insufficient number of lymphocytes-mutation, stress, poor
nutrition
• Immunological surveillance
3. Viral Gene Hypothesis
Viruses are responsible for the Cancer
3. Viral Gene Hypothesis -
Evidences –
1. Demonstration of transmission of leukemia by cell free
filtrates of blood from diseased chicken to healthy
chicken
2. Rous ( 1911) transmitted chicken sarcoma from diseased
chicken to healthy chickens
3. Viruses producing Cancer are called ‘Tumor / Oncogenic
Viruses,
4. Two types – DNA tumor & RNA tumor viruses
5. Common Property- Viral genome integrates into host
chromosomes
Five Groups-
Papova viruses
Adenoviruses
Pox viruses
Herpes viruses
Hepatitis viruses
Among these Papoviruses have received more attension
as they cause tumors in variety of animals
DNA Tumor Viruses
Name derived from first two letters of three viruses-
Papilloma virus
Polyoma virus
Simian vacuolating virus (SV 40)
They belong to papovaviridiae family
It includes two genera- Papiloma & Polyoma
SV40 are now included in Polyoma viruses
All of them are small , naked, icosahedral, circular,
double stranded DNA viruses about 55 nm in diameter
Papova viruses
Papilloma virus is associated with benign warts
Natural infection results in benign warts
Induce tumors only in natural hosts
Transform normal cells into cancer cell in vitro very rarely
Warts are usually benign , but may convert into malignant
carcinomas
Also associated with penile, uterine & cervical cancer
Replicate exclusively in Keratinocytes(Outermost layer
of skin
Polyoma virus – Polyoma means multiple tumors
Do not induce tumors in natural hosts like monkey & mouse
For example- SV 40 do not induce tumor in monkeys
but induce sarcoma in hamster
SV 40 is most thoroughly studied oncogenic DNA virus
Other examples are JC & BK virus
Termed as ‘Oncorna viruses’
Family- Retroviridiae – Retroviruses – icosahedral , enveloped,
two segments of RNA, reverse transcriptase
Five Categories- Based on host range & disease type
Avian leukosis complex – Rous sarcoma virus of
chickens
Murine leukosis virus- Murine lukemia & sarcoma
viruses
Mammary tumor virus of Mice- Bittner virus
Leukosis sarcoma virus- Sarcoma in cats, hamster,
guinea pigs & monkeys
Huan T cell lymphotrophic Virus ( HTLV) – Type 1 & 2
Type 1 causes Adult T cell lymphoma
Type 2 causes hairy cell leukemia (Bone has difficulty in
producing normal WBCs, RBCs & Platelets
RNA Tumor Viruses
1. Oncogene Theory
Proposed by Huebner & Todaro
Genetic information is present in each & every body cell
Transmitted from parents to offspring through germ cells
Infection has occurred millions of years ago during evolution
Thus, every cell is assumed to contain ‘oncogene’
It is normally kept in repressed condition
Derepression by physical, chemical & biological agents
2. Protovirus Theory
Proposed by Temin
 DNA RNA DNA Reintegration into original DNA
Theories of Oncogenesis by RNA Tumor Viruses
Oncogene Theories
3. Provirus Theory
Proposed by Spiegelman
Direct infection with cancer viruses
Transmission is horizontal – from one individual to another
individual through provirus state
Among these oncogene hypothesis is cosistant with number of
observations
THANK YOU………

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Oncogenesis / Carcinogenesis

  • 1. By Dr. G. V. Mali Department of Microbiology Bharati Vidyapeeth’s Matoshri Bayabai Shripatrao Kadam Kanya Mahavidyalaya, Kadegaon Dist. Sangli 8th September 2018
  • 2. Oncogenesis :  Also termed as ‘Carcinogenesis’ – The process of formation of Cancer  Cancer- Latin Word – Meaning is Crab.  Greek Physician Hippocrates – Crab like Disease.  Definition – Abnormal , unregulated and uncontrolled growth of cells – result is lumps or mass of cells  Cancer is also known by the term – Tumor or Malignancy  Tumor is Latin word- means swelling  Suffix ‘-oma’ is used to describe the Tumor
  • 3. Types of Cancer : Classification is done on two Criteria 1. Pattern of Growth i. Benign Tumor ii. Malignant Tumor 2. Types of tissues in which it originates i. Carcinomas ii. Sarcomas iii. Leukemias iv. Lymphomas
  • 4. i. Benign Tumors - • Cancer cells do not invade surrounding tissues • Remain localized as a compact mass • Encapsulated by a membrane called lamina • Grow by displacing surrounding tissues • They are not fatal, however….. • They are usually removed by surgery ii. Malignant Tumors - • Cancer cells invade surrounding tissues, organs & other parts • Capable of invasion and metastasis • Not encapsulated by any membrane • Growth is fast and lethal • Resistant to treatment and may cause death
  • 5.
  • 6. i. Carcinomas- • Cancer of epithelial cells , most common • Accounts for 85 – 90 % of total human cancers • Skin, prostate , bladder , breast , linings of respiratory, gastrointestinal , urinary and genital systems •Two major subtypes- •Adenocarcinoama-develops in organs and glands •Squamous cell carcinoma- in sqamous epithelium ii. Sarcoma - • Cancer of supportive and connective tissues • Bones, cartilages, muscles, blood vessels & tissues at joints • Account for 1 % of total human cancers • Arms , legs, hands , feet , chest , back , hips , shoulder, abdomen, head and neck
  • 7.
  • 8.
  • 9. iii. Leukemias- ( Blood cancer / liquid cancer ) • Cancer of blood forming cells (hematopoietic cells) of bone marrow • Accounts for 4% of total human cancers • Hematopoietic cells produce WBCs • Characterized by overproduction of abnormal & immature WBCs • Such cells do not play role in the defense mechanism of body • Four Types- i. Acute lymphocytic leukemia(ALL)-Cancer of lymphocytes ii.Acute myelogenous leukemia ( AML)- Cancer of granulocytes & monocytes •Chronic lymphocytic leukemia ( CLL) •Chronic myelogenous leukemia ( AML)
  • 10.
  • 11.
  • 12.
  • 13. iv. Lymphomas - • Cancer of lymphatic tissues-lymphocyes, lymph nodes, lymph vessels and lymphoid organs • Accounts for 5% of total human cancers •Two Types- 1. Hodgkin’s Lymphoma – Large, Binuclated cells called Reed- Sternberg cells 2. Non Hodgkin’s Lymphoma – Do not contain Reed- Sternberg cells
  • 14.
  • 15. •Increased production of lytic enzymes •Genetic alterations •Induction of neoplasm in experimental animals •Altered signal transduction mechanism •Alterations in electric charge •Ability to host’s anti-tumor immune response •Alteration in cell membrane structure and functions Characteristics of Cancer Cells •Infinite growth (Immortality) •Metastasis •Invasiveness •Loss of contact inhibition •Loss of anchorage dependence •Reduced serum requirements •Growth factor independence •Loss of cell differentiation •Inhibition of apoptosis •Angiogenesis •Changes in cytoskeleton •Changes in cell morphology and cytology
  • 16. HYPOTHESIS ABOUT CANCER 1. Somatic Mutation Hypothesis i. Mutational activation of repressed genes ii. Mutational blocking of repressed proteins that keep gene in repressed condition iii. Chromosomal abnormalities and cancer go hand in hand 2. Defective Immunity Hypothesis • Insufficient number of lymphocytes-mutation, stress, poor nutrition • Immunological surveillance 3. Viral Gene Hypothesis Viruses are responsible for the Cancer
  • 17. 3. Viral Gene Hypothesis - Evidences – 1. Demonstration of transmission of leukemia by cell free filtrates of blood from diseased chicken to healthy chicken 2. Rous ( 1911) transmitted chicken sarcoma from diseased chicken to healthy chickens 3. Viruses producing Cancer are called ‘Tumor / Oncogenic Viruses, 4. Two types – DNA tumor & RNA tumor viruses 5. Common Property- Viral genome integrates into host chromosomes
  • 18. Five Groups- Papova viruses Adenoviruses Pox viruses Herpes viruses Hepatitis viruses Among these Papoviruses have received more attension as they cause tumors in variety of animals DNA Tumor Viruses
  • 19. Name derived from first two letters of three viruses- Papilloma virus Polyoma virus Simian vacuolating virus (SV 40) They belong to papovaviridiae family It includes two genera- Papiloma & Polyoma SV40 are now included in Polyoma viruses All of them are small , naked, icosahedral, circular, double stranded DNA viruses about 55 nm in diameter Papova viruses
  • 20. Papilloma virus is associated with benign warts Natural infection results in benign warts Induce tumors only in natural hosts Transform normal cells into cancer cell in vitro very rarely Warts are usually benign , but may convert into malignant carcinomas Also associated with penile, uterine & cervical cancer Replicate exclusively in Keratinocytes(Outermost layer of skin Polyoma virus – Polyoma means multiple tumors Do not induce tumors in natural hosts like monkey & mouse For example- SV 40 do not induce tumor in monkeys but induce sarcoma in hamster SV 40 is most thoroughly studied oncogenic DNA virus Other examples are JC & BK virus
  • 21.
  • 22. Termed as ‘Oncorna viruses’ Family- Retroviridiae – Retroviruses – icosahedral , enveloped, two segments of RNA, reverse transcriptase Five Categories- Based on host range & disease type Avian leukosis complex – Rous sarcoma virus of chickens Murine leukosis virus- Murine lukemia & sarcoma viruses Mammary tumor virus of Mice- Bittner virus Leukosis sarcoma virus- Sarcoma in cats, hamster, guinea pigs & monkeys Huan T cell lymphotrophic Virus ( HTLV) – Type 1 & 2 Type 1 causes Adult T cell lymphoma Type 2 causes hairy cell leukemia (Bone has difficulty in producing normal WBCs, RBCs & Platelets RNA Tumor Viruses
  • 23. 1. Oncogene Theory Proposed by Huebner & Todaro Genetic information is present in each & every body cell Transmitted from parents to offspring through germ cells Infection has occurred millions of years ago during evolution Thus, every cell is assumed to contain ‘oncogene’ It is normally kept in repressed condition Derepression by physical, chemical & biological agents 2. Protovirus Theory Proposed by Temin  DNA RNA DNA Reintegration into original DNA Theories of Oncogenesis by RNA Tumor Viruses
  • 25. 3. Provirus Theory Proposed by Spiegelman Direct infection with cancer viruses Transmission is horizontal – from one individual to another individual through provirus state Among these oncogene hypothesis is cosistant with number of observations