The aflatoxins are among the most potent genotoxic agents known [19]. Aflatoxin B1 (AFB1) is produced by the fungi Aspergillus flavus and Aspergillus parasiticus, and contaminates improperly stored rice, corn, and peanuts [8]. It induces various chromosomal aberrations, unsched uled DNA synthesis and chromosomal strand breaks in human cells [19]. Aflatoxin B1 is metabolized by hepatic cytochrome p450 to exo-8,9-epoxide, which is mutagenic [1]. After conversion, AFB1-8,9-epoxide can react with guanine nucleotides in the hepatocyte DNA to form a number of adducts capable of forming subsequent repair-resistant adducts, depurination, or of leading to error-prone DNA repair that results in single-strand breaks, base pair substitutions, or frame shift mutations. The most prevalent aflatoxin-nucleic acid adduct is AFB-N7-guanine, and mispairing of the adduct may induce both transversion and transition mutations [19].

Environmental exposure to hepatic carcinogen AFB1 may cause a specific missense mutation in codon 249 of the p53 tumor-suppressor gene. The most prevalent muta tion induced by aflatoxin in the p53 gene is a GC>TA transversion (arginine.serine alteration in the p53 pro tein) in the third nucleotide of codon 249 [1]. The fre quency of codon 249 mutations parallels the level of afla toxin exposure [20]. Very importantly, AFB1 has syner gistic effects with the HBV that may sensitize hepatocytes to the carcinogenic effects of aflatoxin [21]. Due to the similar frequency of mutations in p53 in regions with a high incidence of HBV and varying aflatoxin exposure, it has been suggested that alterations in p53 independent of the codon 249 mutation may play an important role in HBV-associated HCC. It has been demonstrated that codon 249 is not the major site of adduction by AFB1; adducts were detected in codons in exons 7 and 8. The G>T transversions at the third base of codon 249 were preferentially induced in vitro in human hepatocarcinoma cells incubated with AFB1, although G>T and C>A trans versions were also observed in adjacent codons [20].

The electrophilic intermediates (epoxides), resulting from conversion of AFB1, are detoxified mainly by glutathione-S-transferase (GST) that catalyze the conjuga tion of reduced glutathione to electrophilic centers of the substrates. Activity of the pathways that detoxify the muta genic AFB1-8,9-exo-epoxide can be decreased by poly morphisms of the GST gene [22].

It has been suggested that interaction among the geno types of three enzymes associated with AFB1 metabolism and DNA repair [GSTM1 null genetic polymorphism, megakaryocyte-associated tyrosine kinase (HYL1*2) genotype YH/HH) and X-ray repair complementing defec tive repair in Chinese hamster cells (XRCC1) genotype AG/GG] and AFB1 intake may have functional signifi cance in the repair of AFB1-induced genetic lesions [23].