Chemoprevention of hepatocellular carcinoma in aflatoxin endemic areas
Chemoprevention of hepatocellular carcinoma in aflatoxin endemic areas
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DOI：
10.1053/j.gastro.2004.09.046
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发表时间：
2004-11-01
期刊：
影响因子：
29.4
通讯作者：
Groopman, JD
中科院分区：
文献类型：
--
作者：
Kensler, TW;Egner, PA;Groopman, JD
肝细胞癌是世界范围内最常见的癌症之一。感染B型肝炎病毒和暴露于饮食中的黄曲霉毒素协同作用，以放大风险。从公共卫生的角度来看，肝炎病毒疫苗接种计划和努力，以减少黄曲霉毒素的暴露和减轻不可避免的暴露的毒理学后果应该有重大影响，这种疾病的全球发病率。在实验上，黄曲霉毒素诱导的肝癌发生可以被超过一个分数的不同的化学预防剂具有多种作用机制。其中一种药物，奥替普拉，是一种有效的诱导剂，可以诱导2相酶，参与包括黄曲霉毒素在内的致癌物的解毒。第二种药剂叶绿酸通过形成分子复合物阻碍致癌物的生物利用度，并增强其在粪便流中的消除。这篇综述强调了最近的随机临床试验的结果与oltipraz和叶绿酸在个人暴露于饮食黄曲霉毒素和肝癌的高风险发展。两种化学预防剂都以与保护一致的方式调节了研究参与者中黄曲霉毒素生物标志物的水平。虽然药理学方法建立了原则证据，并帮助确定干预的关键分子靶点，但也使用这些分子靶点的基于食物的方法可能是在高危人群中广泛应用的最实用的方法。
Hepatocellular carcinoma is one of the most common cancers worldwide. Infection with hepatitis B virus and exposure to aflatoxins in the diet act synergistically to amplify risk. From a public health perspective, hepatitis virus vaccination programs and efforts to both reduce aflatoxin exposures and to attenuate the toxicological consequences of unavoidable exposures should have major impacts on the global incidence of this disease. Experimentally, aflatoxin-induced hepatocarcinogenesis can be inhibited by over a score of different chemopreventive agents with multiple mechanisms of action. One agent, oltipraz, is a potent inducer of phase 2 enzymes involved in the detoxication of carcinogens including aflatoxin. A second agent, chlorophyllin, impedes the bioavailability of carcinogens by forming molecular complexes and enhances their elimination in the fecal stream. This review highlights the findings of recent randomized clinical trials with oltipraz and chlorophyllin conducted in individuals exposed to dietary aflatoxins and at high risk for development of liver cancer. Both chemopreventive agents modulated levels of aflatoxin biomarkers in the study participants in manners consonant with protection. Although pharmacological approaches establish proof of principle and help identify key molecular targets for interventions, food-based approaches that also use these molecular targets may be the most practical for widespread application in high-risk populations.