Molecular biomarkers for aflatoxins: From adducts to gene mutations to human liver cancer
Molecular biomarkers for aflatoxins: From adducts to gene mutations to human liver cancer
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DOI：
10.1139/cjpp-74-2-203
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发表时间：
1996-02-01
影响因子：
2.1
通讯作者：
Scholl, P
中科院分区：
文献类型：
--
作者：
Groopman, JD;Wang, JS;Scholl, P
在过去的30年里，人们进行了广泛的努力来研究黄曲霉毒素暴露与人类肝癌之间的关系。这些研究一直受到阻碍，缺乏足够的剂量学数据的黄曲霉毒素的摄入量，排泄量和代谢的人，以及由全球癌症发病率和死亡率统计数据的质量普遍较差。这些现实促使人们努力开发新技术来评估黄曲霉毒素的暴露状况和风险，这些物质是少数几种尝试进行定量风险评估的环境致癌物之一。这些风险评估的目标之一是开发初级酸二级预防干预方法，以降低黄曲霉毒素暴露对人类健康的影响。本文所述研究的长期目标是将生物标志物应用于开发用于癌症高危人群的预防性干预措施。几种黄曲霉毒素特异性生物标志物已在流行病学研究中得到验证，现在可用作预防试验中的中间生物标志物。这些黄曲霉毒素生物标志物的开发是基于从实验和人体研究中收集的黄曲霉毒素的生物化学和毒理学知识。这些生物标志物随后被用于实验模型中，以提供有关不同疾病风险情况下标志物调节的数据。这种系统性的方法为预防性干预措施提供了鼓励，并应作为开发和验证其他化学特异性生物标志物及其在癌症或其他慢性疾病中的应用的模板。
Over the past 30 years there have been extensive efforts to investigate the association between aflatoxin exposure and human liver cancer. These studies have been hindered by the lack of adequate dosimetry data on aflatoxin intake, excretion, and metabolism in people, as well as by the general poor quality of worldwide cancer morbidity and mortality statistics. These realities have spurred the efforts to develop new technologies to assess exposure status and risk for aflatoxins, and these agents are among the few environmental carcinogens for which quantitative risk assessments have been attempted. One of the goals of these risk assessments has been the development of primary acid secondary preventive intervention methods to lower the human health impact from aflatoxin exposures. The long-term goal of the research described herein is the application of biomarkers to the development of preventive interventions for use in human populations at high risk for cancer. Several of the aflatoxin-specific biomarkers have been validated in epidemiologic studies and are now available for use as intermediate biomarkers in prevention trials. The development of these aflatoxin biomarkers has been based upon the knowledge of the biochemistry and toxicology of aflatoxins gleaned from both experimental and human studies. These biomarkers have been utilized subsequently in experimental models to provide data on the modulation of the markers under different situations of disease risk. This systematic approach provides encouragement for preventive interventions and should serve as a template for the development and validation of other chemical-specific biomarkers and their application to cancer or other chronic diseases.