Benzo[a]pyrene

• B[a]P

  • one of polycyclic aromatic hydrocarbon
  • high in cigarette smoke, diesel exhaust, charcoal-based foods
  • readily absorbed by ingestion + inhalation + skin
• metabolized by cytochroms p450 --> carcinogenic metabolite (BPDE) --> creates DNA adduct
• • indicator of air qiality
  • EU standard: < 1 ng/ m3
• • Metabolism of B[a]P involves the activity of cytochrome P450 (CYP1 family) + microsomal epoxide hydrolase
  • Cytochrome P4501 A1 (CYP1A1) is believed to play the most important role in the pro- carcinogenic B[a]P activation
• Biotransformation

  • Involve CYP1A1 + Microsomal Epoxide Hydroxylase
• B[a]P --> CYP1A1 --> Epoxide Hydroxylase --> CYP1A1 --> add on nucleotide (Guanine at position 2) --> N2 Guanine adduct
• • K-RAS and p53: mutated in smoking-related lung cancers
  • The guanine adduct is misread as a thymine by the DNA polymerase during replication
  • the original G—C base pair may be replaced by a T—A base pair