AFB1epoxid

AFB1-8,9-epoxide, commonly referred to as aflatoxin B1 epoxide, is the reactive metabolite formed from aflatoxin B1 (AFB1) in mammalian livers. It is considered the ultimate carcinogenic form of aflatoxin B1 because of its high reactivity toward DNA.

Biotransformation of AFB1 to the 8,9-epoxide is mediated by hepatic cytochrome P450 enzymes, notably CYP1A2 and CYP3A4 in humans. The epoxide exists as two stereoisomers, with the exo-epoxide typically more reactive toward nucleophiles. As an electrophile, it readily attacks the N7 position of guanine in DNA, forming AFB1-N7-guanine adducts and related lesions. These adducts can cause miscoding during replication, contributing to G:C to T:A transversions and adopting mutational hotspots associated with hepatocellular carcinoma in exposed individuals.

Exposure to AFB1-epoxide-bearing DNA damage is a major health concern in settings where aflatoxin-contaminated foods are common, such as stored maize, peanuts, and tree nuts. The epoxide’s genotoxicity has been demonstrated in animal studies and through biomarkers detected in humans. AFB1 exposure is strongly linked to hepatocellular carcinoma, and risk is heightened by chronic hepatitis B virus infection. The International Agency for Research on Cancer classifies aflatoxin B1 as a Group 1 carcinogen.

Detoxification pathways mitigate epoxide injury: epoxide hydrolase converts the epoxide to a less reactive dihydrodiol, and glutathione S-transferases can conjugate the epoxide with glutathione for excretion. Individual variation in these enzymes influences susceptibility to aflatoxin-related DNA damage. Biomarkers such as AFB1-lysine adducts and urinary AFB1-N7-guanine are used to assess exposure.