Pathology · Neoplasia (Classification, Carcinogenesis, Tumor Markers, Paraneoplastic)

Aflatoxin B1, produced by Aspergillus flavus contaminating stored grains and peanuts, is a well-established chemical carcinogen. Its hepatocarcinogenic effect is mediated by:

  • A Induction of oxidative stress leading to random point mutations throughout the genome
  • B Direct inhibition of nucleotide excision repair enzymes
  • C Formation of DNA adducts that cause a characteristic mutation at codon 249 of the TP53 gene
  • D Covalent binding to the O6 position of guanine, mimicking a base analog during replication
Correct answer: C. Formation of DNA adducts that cause a characteristic mutation at codon 249 of the TP53 gene

Explanation

Aflatoxin B1 is metabolized by cytochrome P450 to an epoxide that forms adducts at the N7 position of guanine, producing a characteristic G:A to T:C transversion at codon 249 of TP53, a signature finding in hepatocellular carcinoma from high-exposure regions such as sub-Saharan Africa and China. Option D describes alkylating agents like nitrosamines acting at O6 guanine, a different mechanism. Synergy with chronic hepatitis B greatly increases risk.

Reference: Robbins and Cotran Pathologic Basis of Disease, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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