Polycyclic aromatic hydrocarbons
Summary
Polycyclic aromatic hydrocarbons (PAHs) are fused-ring organic carcinogens generated by incomplete combustion of organic material (tobacco smoke, charred meat, soot, fossil fuels). They are bioactivated by CYP450 to DNA-binding epoxides causing mutations in lung, skin, and bladder cancers.
Detail
Classic PAHs include benzo[a]pyrene (a major carcinogen in tobacco smoke), and the historical mixture in soot that caused scrotal squamous cell carcinoma in chimney sweeps (Percival Pott, 1775 -- the first occupational cancer described). CYP1A1 metabolizes PAHs to reactive diol-epoxides that form bulky DNA adducts at guanine residues, repaired by nucleotide excision repair (defective in xeroderma pigmentosum). Benzo[a]pyrene specifically induces G:C -> T:A transversions in TP53 hotspots in lung cancer. Disease associations: bronchogenic carcinoma (especially squamous and small cell), bladder transitional cell carcinoma, gastric cancer (smoked/grilled foods), and skin cancer. PAHs also induce their own metabolism via AhR -> CYP1A1.
Sources
- First Aid for USMLE Step 1 2024
- Robbins Basic Pathology 10th ed
- Goljan Rapid Review Pathology
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