Chemical carcinogens

Direct acting

Indirectly acting:

Procarcinogen → Ultimate carcinogen (via CYP 450 enzymes)

Adduct formation with Purines, Pyrimidines

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Breakage of phosphodiester bonds

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Mutations: It is a stable and heritable genetic change that occurs spontaneously and randomly among organisms.

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Cancer/Neoplasia: An abnormal mass of tissue the growth of which is excessive and uncoordinated with that of normal tissue and continues in the same excessive manner after removal of stimulus which evoked that change.

1. In-vitro carcinogenicity testing of a chemical using histidine deficient strains of S.typhimurium
2. Addition of chemical carcinogens causes mutations (reverse mutation)restoring the ability of the bacteria to synthesize histidine (His+).
3. By detecting the strain of Salmonella (His+) in the colonies of agar plates,the chemical mutagens can be identified (80% specificity).
4. This is followed by animal carcinogenicity testing.

• Substances which enhance carcinogenicity of chemical agents which by themselves are non-carcinogenic.

Eg. Initiating agent: Benzo(a)pyrene          

       Promoting agent: Croton oil                  ( Skin Cancer)

       Other Promoters: Saccharin, Phenobarbital