Department of Medicine, Groote Schuur Hospital, University of Cape Town, Cape Town, and Department of Medicine University of the Witwatersrand Johannesburg, South Africa; Email:
J Gastrointestin Liver Dis. 2013 Sep;22(3):305-10.
Aflatoxins, metabolites of the fungi Aspergillus flavus and Aspergillus parasiticus, are frequent contaminants of a number of staple foods, particularly maize and ground nuts, in subsistence farming communities in tropical and sub-tropical climates in sub-Saharan Africa, Eastern Asia and parts of South America. Contamination of foods occurs during growth and as a result of storage in deficient or inappropriate facilities. These toxins pose serious public health hazards, including the causation of hepatocellular carcinoma by aflatoxin B1. Exposure begins in utero and is life-long. The innocuous parent molecule of the fungus is converted by members of the cytochrome p450 family into mutagenic and carcinogenic intermediates. Aflatoxin-B1 is converted into aflatoxin B1-8,9 exo-epoxide, which is in turn converted into 8,9-dihydroxy-8-(N7) guanyl-9-hydroxy aflatoxin B1 adduct. This adduct is metabolized into aflatoxin B1 formaminopyrimidine adduct. These adducts are mutagenic and carcinogenic. In addition, an arginine to serine mutation at codon 249 of the p53 tumor suppressor gene is produced, abrogating the function of the tumor suppressor gene, and contributing to hepatocarcinogenesis. Aflatoxin B1 acts synergistically with hepatitis B virus in causing hepatocellular carcinoma. A number of interactions between the two carcinogens may be responsible for this action, including integration of hepatitis B virus x gene and its consequences, as well as interference with nucleotide excision repair, activation of p21waf1/cip1, generation of DNA mutations, and altered methylation of genes. But much remains to be learnt about the precise pathogenetic mechanisms responsible for aflatoxin B1-induced hepatocellular carcinoma as well as the interaction between the toxin and hepatitis B virus in causing the tumor.
黄曲霉毒素是黄曲霉菌和寄生曲霉菌的真菌代谢物，是热带和亚热带气候下的撒哈拉以南非洲、东亚和南美洲部分地区自给农业社区中，多种主食（尤其是玉米和花生）的常见污染物。在生长过程中以及由于在不足或不当的设施中储存而导致食物受到污染。这些毒素对公共健康构成严重危害，包括黄曲霉毒素 B1 导致的肝细胞癌。暴露始于胎儿期，并持续终生。真菌的无毒母体分子被细胞色素 p450 家族的成员转化为诱变和致癌的中间产物。黄曲霉毒素 B1 转化为黄曲霉毒素 B1-8,9 外环氧，再转化为 8,9-二羟基-8-（N7）鸟苷-9-羟基黄曲霉毒素 B1 加合物。该加合物被代谢为黄曲霉毒素 B1 甲酰嘧啶加合物。这些加合物具有致突变性和致癌性。此外，p53 肿瘤抑制基因的密码子 249 处的精氨酸到丝氨酸突变产生，导致肿瘤抑制基因功能丧失，并促进肝癌发生。黄曲霉毒素 B1 与乙型肝炎病毒协同作用导致肝细胞癌。两种致癌物之间可能存在多种相互作用，包括乙型肝炎病毒 x 基因及其后果的整合，以及对核苷酸切除修复的干扰、p21waf1/cip1 的激活、DNA 突变的产生以及基因的甲基化改变。但是，对于黄曲霉毒素 B1 诱导的肝细胞癌的确切发病机制以及毒素与乙型肝炎病毒在导致肿瘤方面的相互作用，仍有许多需要了解。
