Question

(a) Outline the two stage process of genotoxic carcinogenesis. (3 marks) (b) Explain why benzo[a]pyrene (structure below), a constituent of cigarette smoke, causes lung cancer. (3 marks) Benzo[a]pyrene (c) Why is 2-aminonaphthalene (2-napthylamine; structure below) a specific bladder carcinogen. (4 marks) NH2 2-aminonaphthalene

Answer 1

& There are two stages of genetoric careenogenesis process : (1) Promotion (2) Progression 2) (1) Promotion : It does not involve changes. in the structure of DNA. But it involves. in the expression of the genome mediated through promoter - receptor interactions. 2 (2) Progression in It is the final irreversible stage of genetoxic carcenogenesis. It is characterized by karyotypic instability and malignant growth. A Benzo [a] pyrene is a Polycyclic Aromatic Hydrocarbon. 2) Generally in polycyclic aromatic hydrocarbons contains a bay region and are oxidized by mammalian metabolic enzymes and these oxidized products are called as carcenogens. Bay orol region ... Hoe [oolo Ho

2 I > In this process two cytochrome 1450 enzymes are involved. (i) CYPLAL and (ii) CYPLAZ. These enzymes are known to oxidize benzo- [a] pyrene to benzo [a] pyrene did epoxide (BPDE). B.PDE binds selectively to the minor groove because BPDE alkylates the 2-amino group of gar guanine bases. . As a result of alkylation in DNA the strand is miscopied, leading to a transversions. 2

roll og region enzyme CYPLA Holm ani ne on J CYPLA CYPLA a base of DNA DNA DNA you on в РФЕ on

4-13) & The 2-amine naphthalene can be hydroxylated by cytochrome 2-450 enzyme and the new or group undergo gueuronidation. This reaction increase the solubility of 2-aminonaphthalene in urine for excretion! 3 The glucon glucuronidated product hydsolyse at are usine pH and from glucuronic acid and the new chemical can bind to DNA-forming addicts in bladder. 2. This in mutation leads to bladder cancer. Glucuronosyl transferase -o-glucuronic acid glucuronic acid At urine ph Bladder cancer