Which of the following carcinogens exerts its effect primarily via formation of a covalent adduct with guanine residues in DNA, without requiring prior metabolic activation?
- A Benzo[a]pyrene
- B Nitrogen mustard (mechlorethamine) ✓
- C Aflatoxin B1
- D Dimethylnitrosamine
Correct answer: B. Nitrogen mustard (mechlorethamine)
Explanation
Nitrogen mustard is a direct-acting alkylating carcinogen/cytotoxic agent that spontaneously forms a reactive ethylenimonium ion, which alkylates guanine at the N7 position without requiring metabolic activation — these are termed 'direct-acting' or 'ultimate carcinogens' as supplied. Benzo[a]pyrene, aflatoxin B1, and dimethylnitrosamine are procarcinogens requiring CYP450-mediated metabolic activation to their ultimate carcinogenic forms before forming DNA adducts.
Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.
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