Wild C P, Turner P C
Molecular Epidemiology Unit, Epidemiology and Health Services Research, Algernon Firth Building, School of Medicine, University of Leeds, Leeds LS2 9JT, UK.
Mutagenesis. 2002 Nov;17(6):471-81. doi: 10.1093/mutage/17.6.471.
Aflatoxins have been extensively studied with respect to their mechanisms of toxicity. An understanding of metabolism, DNA adduct induction, mutagenicity and carcinogenicity has been paralleled by the development of biomarkers of aflatoxin exposure and biological effects (e.g. mutations) applied to human populations. The improvements in exposure assessment and their application in prospective epidemiological studies and the demonstration of a specific mutation in the TP53 gene in hepatocellular carcinomas from areas of high aflatoxin exposure have contributed significantly to the classification of aflatoxins as human carcinogens. In addition to establishing the carcinogenicity of aflatoxins in humans, understanding molecular mechanisms of action has provided the scientific rationale for prevention strategies, including primary and chemoprevention approaches. Overall, integrated, multidisciplinary research on aflatoxins has provided the platform on which to base decisions regarding acceptable exposures and priorities for interventions to reduce human risk in a public health context.
黄曲霉毒素的毒性机制已得到广泛研究。随着黄曲霉毒素暴露生物标志物以及应用于人群的生物效应（如突变）生物标志物的发展，人们对其代谢、DNA加合物诱导、致突变性和致癌性有了更深入的了解。暴露评估的改进及其在前瞻性流行病学研究中的应用，以及在黄曲霉毒素高暴露地区肝细胞癌中TP53基因特定突变的发现，为将黄曲霉毒素归类为人类致癌物做出了重要贡献。除了确定黄曲霉毒素对人类的致癌性外，了解其分子作用机制还为预防策略提供了科学依据，包括一级预防和化学预防方法。总体而言，对黄曲霉毒素进行的综合多学科研究提供了一个平台，在此基础上可做出关于可接受暴露水平的决策以及在公共卫生背景下降低人类风险的干预重点。
