McLean M, Dutton M F
Department of Physiology, Faculty of Medicine, University of Natal, Congella, Durban, South Africa.
Pharmacol Ther. 1995 Feb;65(2):163-92. doi: 10.1016/0163-7258(94)00054-7.
The aflatoxins are a group of closely related mycotoxins that are widely distributed in nature. The most important of the group is aflatoxin B1 (AFB1), which has a range of biological activities, including acute toxicity, teratogenicity, mutagenicity and carcinogenicity. In order for AFB1 to exert its effects, it must be converted to its reactive 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 can form derivatives with several cellular macromolecules, including DNA, RNA and protein. Cytochrome P450 enzymes may additionally catalyse the hydroxylation (to AFQ1 and AFM1) and demethylation (to AFP1) of the parent AFB1 molecule, resulting in products less toxic than AFB1. Conjugation of AFB1 to glutathione (mediated by glutathione S-transferase) and its subsequent excretion is regarded as an important detoxification pathway in animals. Resistance to AFB1 toxicity has been interpreted in terms of levels and activities of these detoxifying pathways. This article reviews the multiple reactions and effects attributed 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 hepatocellular carcinoma (HCC). The anti-mutagenic properties of several dietary factors are also considered in this article. Undoubtedly, the most important aspect of aflatoxin action is its putative role in the development of human cancer, in particular, HCC. Recently, there has been a renewed interest in this aspect and experimental evidence is rapidly accumulating at the molecular level, indicating aflatoxin as an important consideration in the aetiology of human HCC.
黄曲霉毒素是一组密切相关的霉菌毒素，在自然界中广泛分布。该组中最重要的是黄曲霉毒素B1（AFB1），它具有一系列生物活性，包括急性毒性、致畸性、致突变性和致癌性。为了使AFB1发挥其作用，它必须通过受影响动物组织（特别是肝脏）中的混合功能单加氧酶系统（细胞色素P450依赖性）的作用转化为其活性环氧化物。这种环氧化物具有高度反应性，可与包括DNA、RNA和蛋白质在内的几种细胞大分子形成衍生物。细胞色素P450酶还可能催化母体AFB1分子的羟基化（生成AFQ1和AFM1）和去甲基化（生成AFP1），从而产生毒性低于AFB1的产物。AFB1与谷胱甘肽的结合（由谷胱甘肽S-转移酶介导）及其随后的排泄被认为是动物体内重要的解毒途径。对AFB1毒性的抗性已根据这些解毒途径的水平和活性来解释。本文综述了黄曲霉毒素的多种反应和作用，特别提及黄曲霉毒素与核酸和蛋白质的相互作用，以及这种霉菌毒素在疾病发展和肝细胞癌（HCC）促进中的作用。本文还考虑了几种膳食因素的抗诱变特性。毫无疑问，黄曲霉毒素作用的最重要方面是其在人类癌症，特别是HCC发展中的假定作用。最近，人们对这方面重新产生了兴趣，并且在分子水平上的实验证据正在迅速积累，表明黄曲霉毒素是人类HCC病因学中的一个重要考虑因素。
