Aflatoxin

• Carcinogen found in tabacco products & smoke
• • Secondary metabolites produced by diff strains of fungi
  • Aspergillus flavus: abundant in warn and humid climate area
• • Contaminants in crops (Maize, Peanuts, Cereals, Tree nuts, Spices)
  • b/c environmental factors + improper harvesting and storage practices
• • Strong thermal stability even at > 100 oC
  • cannot be removed by heat or sterilization
• • Chronic exposure: Liver cancer
  • If infected with Hepatitis B virus --> further increase risk of liver cancer in AFB1 exposed people
• Aflatoxin transferred to offspring during gestation and lactation (upon consumption of contaminated products)
• If cows/ chicken fed contaminated food --> Aflatoxin stay in their body --> milk and eggs consumed by humans --> transfer
• Types of Aflatoxin

  • 4 major types: B1, B2, G1, G2
  • B1, B2 hydroxylated --> M1, M2
  • B1 = Group 1 carcinogen; Liver cancer
  • M1 = Group 2B
• Metabolism of Aflatoxin (needs activation)

  • Aflatoxin B1 activated by CYP450/ Prostaglandin H Synthase (PGH) --> AFB1 - 8, 9 - Epoxide (toxic) + Hydroxylated metabolites [AFQ1 & AFM1] --> DNA adduct [AFB1 - N7 - Gua] (interact with guanine at position 7)
  • AFB1 - 8, 9 - Epoxide conjugate with Glutathione (reduce toxicity by GST)
• • AFB1 - 8, 9 - Epoxide: Damage protein --> Acute toxicity
  • AFB1 --> Reactive oxygen species --> Cancer
  • AFB1 --> Lipid peroxidase --> Cancer
• Genotoxicity of Aflatoxin

  • Alternative: Lipid peroxidase = responsible for AFB1 carcinogenesis
  • In an in vitro study, AFB1 induced 2 types of DNA adducts in human hepatocytes
  • AFB1 - 8, 9 - Epoxide - deoxyganosine
  • meth - OH - PdG (induced by lipid peroxidation byproducts): DNA repair is poor, mutation occur at p53 tumor suppressor gene; LPO byproducts inhibit DNA repair (nucleotide excision repair + base excision repair)