Shank R C
J Toxicol Environ Health. 1977 Jul;2(6):1229-44. doi: 10.1080/15287397709529526.
Aflatoxins are associated with acute toxicoses in poultry and livestock and with liver cancer in human populations in Africa and Southeast Asia. Comparative metabolism studies indicate that aflatoxin B1, the most potent of these compounds, requires metabolic activation to the ultimate carcinogen. The mycotoxin (1) is oxidatively demethylated to form the phenolic derivative, (2) is hydroxylated directly at three sites, and (3) undergoes reduction of the carbonyl group in the cyclopentenone ring to a hydroxyl group; these five hydroxy derivatives all appear to be part of detoxication pathways. Considerable evidence is now available to support the hypothesis that activation of aflatoxin B1 to the ultimate carcinogen involves epoxidation of the double bond in the terminal furan ring. The epoxide decomposes to form a carbonium ion at C-2, which attacks nucleophilic sites in DNA, especially on the guanine moiety. Thus, like carcinogenic polycyclic hydrocarbons and N-nitroso compounds, aflatoxin B1 appears to be activated to an alkylating agent.
黄曲霉毒素与家禽和家畜的急性中毒以及非洲和东南亚人群的肝癌有关。比较代谢研究表明，这些化合物中最具毒性的黄曲霉毒素B1需要代谢激活才能形成最终致癌物。这种霉菌毒素（1）发生氧化脱甲基反应形成酚类衍生物，（2）直接在三个位点发生羟基化，（3）环戊烯酮环中的羰基还原为羟基；这五种羟基衍生物似乎都是解毒途径的一部分。现在有大量证据支持黄曲霉毒素B1激活形成最终致癌物涉及末端呋喃环中双键环氧化的假说。环氧化物分解在C-2处形成碳正离子，其攻击DNA中的亲核位点，尤其是鸟嘌呤部分。因此，与致癌多环烃和N-亚硝基化合物一样，黄曲霉毒素B1似乎被激活成为一种烷基化剂。
