An epidemiological study links dietary contamination of maize and groundnuts with a specific mutational signature in hepatocellular carcinoma occurring in regions of sub-Saharan Africa and China. The causative mycotoxin and its molecular target are:
- A Ochratoxin A causing AP-1 activation
- B Fumonisin B1 causing sphingolipid depletion
- C Aflatoxin B1 causing G:C to T:A transversion at codon 249 of TP53 ✓
- D Deoxynivalenol causing ribosomal stress and MYC activation
Correct answer: C. Aflatoxin B1 causing G:C to T:A transversion at codon 249 of TP53
Explanation
Aflatoxin B1, produced by Aspergillus flavus contaminating stored grains and nuts, is metabolized by hepatic cytochrome P450 to an epoxide that forms adducts at guanine residues. The signature lesion is the G:C to T:A transversion at codon 249 of TP53 (the 'third base' mutation), found in a large fraction of hepatocellular carcinomas in high-exposure areas and acting synergistically with chronic hepatitis B infection. The other mycotoxins listed are nephrotoxic or cause food-borne illness without this mutational signature.
Reference: Robbins and Cotran Pathologic Basis of Disease, 10th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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