CELLULAR INTERACTIONS AND METABOLISM OF AFLATOXIN - AN UPDATE

The aflatoxins are a group of closely related mycotoxins that are wide ly distributed in nature. The most important of the group is aflatoxin B-1 (AFB(1)), which has a range of biological activities, including a cute toxicity, teratogenicity, mutagenicity and carcinogenicity. In or der for AFB(1) to exert its effects, it must be converted to its react ive epoxide by the action of the mixed function mono-oxygenase enzyme systems (cytochrome P450-dependent) in the tissues (in particular, the liver) of the affected animal. This epoxide is highly reactive and ca n form derivatives with several cellular macromolecules, including DNA , RNA and protein. Cytochrome P450 enzymes may additionally catalyse t he hydroxylation (to AFQ(1) and AFM(1)) and demethylation (to AFP(1)) of the parent AFB(1) molecule, resulting in products less toxic than A FB(1). Conjugation of AFB(1) to glutathione (mediated by glutathione S -transferase) and its subsequent excretion is regarded as an important detoxification pathway in animals. Resistance to AFB(1) toxicity has been interpreted in terms of levels and activities of these detoxifyin g pathways. This article reviews the multiple reactions and effects at tributed to aflatoxin, with particular reference to the interaction of aflatoxin with nucleic acids and proteins, and the contribution this mycotoxin has in disease development and in the promotion of hepatocel lular carcinoma (HCC). The anti-mutagenic properties of several dietar y factors are also considered in this article. Undoubtedly, the most i mportant aspect of aflatoxin action is its putative role in the develo pment of human cancer, in particular, HCC. Recently, there has been a renewed interest in this aspect and experimental evidence is rapidly a ccumulating at the molecular level, indicating aflatoxin as an importa nt consideration in the aetiology of human HCC.