CARCINOGENESIS
1) CARCINOGENESIS / ONCOGENESIS /
TUMORIGENESIS means Mechanism of
Induction of tumors (pathogenesis of cancer).
2) Agents which can induce tumors are called
Carcinogens (etiology of cancer)
Carcinogenic agent
Mutation/
Chromosomal
translocation
CARCINOGENESIS
Etiology and pathogenesis of cancer can
discussed under following 3 headings
1) CHEMICAL CARCINOGENS & CHEMICAL
CARCINOGENESIS
2) PHYSICAL CARCINOGENS & PHYSICAL
CARCINOGENESIS
3) BIOLOGIC CARCINOGENS & VIRAL ONCOGENES
CHEMICAL CARCINOGENS &
CARCINOGENESIS
Chemical Carcinogenesis
Depending upon mode of action of carcinogenic chemicals they are
divided into 2 broad groups
A. INITIATORS
1)DIRECT- ACTING 2) INDIRECT- ACTING CARCINOGEN
CARCINOGENS (a) Polycyclic Aromatic Hydrocarbons
(a) Alkylating agents Eg : Tobacco ,
Smoke ,
Anti -cancer drugs Fossil fuel ,
Beta -propiolactone mineral oil
(b) Azo- dyes
Epoxides Eg: Butter yellow ,
(b) Acylating agents Scarlet red
(c) Naturally - occurring products
Acetyl imidazole Eg : Safrole
Dimethyl carbamyl chloride A latoxin Bl
Betel nuts
B. PROMOTER CARCINOGEN
- Dietary fat in cancer of colon
- Endogenous or Exogenous oestrogen
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Stages of chemical carcinogenesis /
Pathogenesis of chemical carcinogenesis
Chemical carcinogenesis occurs by induction of mutation
in the Proto- oncogenes & Anti- oncogenes
Chemical carcinogenesis can be learned in 3 steps :
(1) INITIATION OF CARCINOGENESIS
(2) PROMOTION OF CARCINOGENESIS
(3)PROGRESSION OF CARCINOGENESIS
1. INITIATION OF CARCINOGENESIS
Pathogenesis is di erent with direct & indirect carcinogen
DIRECT CARCINOGEN DNA DAMAGE
( ELECTRONPHILIC)
INDIRECT CARCINOGEN ACTIVE CARCINOGEN DNA
(INACTIVE FORM ) ACTIVATION (ELECTRONPHLIC) DAMAGE
IN LIVER
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2. Promotion of Carcinogensis
Promotion is the next sequential stage in the chemical carcinogenesis
Promotors are chemical substance which lack intrinsic carcinogenic
potential but their application subsequent to initiator exposure help the
initiated cell to proliferate
Promotors carcinogenesis are substances such as :
-Esters
-Phenols
-Hormone
-Drugs like Phenolborbitals
3. Progression of Carcinogenesis
Progression of the cancer is the stage when mutated &
proliferated cells show phenotypic feature of malignancy that
includes morphological, biochemical &Molecular characteristics
Such phenotypic feature appears only when the initiated cells
proliferate rapidly & during the process acquire additional
multiple mutations
CELL DIVISION
DNA DAMAGE CELL DIVISION
CELL DIVISION
CHEMICAL CARCINOGENESIS
PHYSICAL CARCINOGEN &
CARCINOGENESIS
Physical carcinogens are divided into 2 groups:
A). RADIATION PHYSICAL AGENTS
The 2 main forms of radiation carcinogens which can induce
cancer
1). ULTRAVIOLET (UV) LIGHT
2). IONISING RADIATION
B). NON -RADIATION PHYSICAL AGENTS
1) GALL STONES
2) HEALED SCARS
3)ASBESTOSIS
A. RADIATION PHYSICAL AGENT
1) ULTRAVIOLET LIGHT
- The main source of UV radiation is the sunlight others are UV
lamps & welders arcs
- In humans , excessive exposure to UV rays can cause various forms of skin cancer
SQUAMOUS CELL CARCINOMA
BASAL CELL CARCINOMA
MALIGNANT MELANOMA
- UV radiation may have various e ects on the cells :
INDUCTION OF MUTATIONS
INHIBITION OF CELL DIVISION
INACTIVATION OF ENZYME
FORMATION OF PYRIMIDINE DIMER IN DNA
2) IONIZING RADIATION
Ionizing radiation is any type of particle or electromagnetic wave that carries enough energy to ionize or remove electrons from an
atom
EG: X-RAYS
ALPHA RAYS
BETA RAYS
GAMMA RAYS
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B. NON - RADIATION PHYSICAL AGENTS
Mechanical injury to the tissue or prolonged contact with certain
physical agents has been observed to have higher incidence of
certain cancer
EG :GALLSTONES :Stones in the gallbladder &in the urinary tract
having higher incidence of cancers these organs
HEALED SCARS : Healed scars following burns or trauma for
increased risk of carcinoma of a ected skin
ASBESTOSIS : Occupational exposure asbestos associated with
asbestos-associated tumors of lung &malignant
mesothelioma of the pleura
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BIOLOGICAL CARCINOGEN &
CARCINOGENESIS
-Various biological agents like VIRUSES,PARASITES,FUNGI,
BACTERIA are implicated in etiology of cancer
-However the Role of viruses in the causation of cancer is more
signi icant.
- Therefore biologic carcinogenesis is largely VIRAL CARCINOGENESIS
- EG OF BIOLOGICAL CARCINOGEN:
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ONCOGENIC VIRUSES :
- oncogenic viruses are of 2 types
(1) DNA ONCOGENIC VIRUSES (2) RNA ONCOGENIC VIRUSES
VIRAL ONCOGENESIS
1. MODE OF DNA VIRAL ONCOGENESIS
- Host cells infected by DNA oncogenic viruses may have one of
the following 2 results
2. MODE OF RNA VIRAL ONCOGENESIS
-All oncogenic RNA viruses are RETROVIRUSES
-A retrovirus is a type of RNA virus that inserts a copy
of it’s genome into the DNA of a host cell that it
invades thus changing the genome of that cell
-Retroviruses contain 2 identical strands of RNA and
the enzyme , reverse transcriptase
STEPS 1 : The RNA virus invades the host cell .The viral envelope fuses with the
Plasma membrane of the host cell viral RNA genome as well as reverse
transcriptase are released into the cytosol
STEP 2 : Reverse transcriptase acts as template to synthesize single strand of
matching viral DNA which is then copied to form complementary DNA resulting
in double- stranded viral DNA
STEP 3 : The provirus is integrated into the cell genome
producing transformed host cell
STEP 4 : Integration of the provirus brings about
replication of viral components which are
then assembled &released by budding
RETROVIRUSES
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