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用于研究致癌过程中毒理学影响的暴露生物标志物。

Exposure biomarkers for the study of toxicological impact on carcinogenic processes.

作者信息

Farmer Peter B

机构信息

MRC Toxicology Unit, University of Leicester, UK.

出版信息

IARC Sci Publ. 2004(157):71-90.

Abstract

Exposure biomarkers for carcinogens in humans include the measurement of the genotoxin or its active metabolite in blood, urine or other tissues, and the determination of the interaction products (adducts) of the carcinogen with protein or DNA. The latter approach may indicate the amount of genotoxically active material that has reached the tissue under study and provides invaluable information for molecular epidemiological studies. Protein adducts are not repaired and are considered primarily as exposure monitors, but DNA adducts may give further information about the mutagenic significance of the exposure. The techniques available for measurement of protein and DNA adducts include mass spectrometry, immunoassay, high performance liquid chromatography with UV, fluorescence or electrochemical detection, 32P-postlabelling (for DNA only) and accelerator mass spectrometry. The lowest limits of sensitivity of the protein adduct measurements is less than 1 pmol adduct/g protein, and the procedures for DNA adduct determination have sensitivities ranging from of 1 adduct in 10(8) to 1 in 10(11) nucleotides. All these techniques are capable of measuring environmental, occupational and dietary exposures to a variety of genotoxic compounds, as exemplified in this review.

摘要

人体致癌物的暴露生物标志物包括在血液、尿液或其他组织中对基因毒素或其活性代谢物的测量,以及对致癌物与蛋白质或DNA的相互作用产物(加合物)的测定。后一种方法可以表明已到达所研究组织的具有基因毒性活性的物质的量,并为分子流行病学研究提供极有价值的信息。蛋白质加合物不会被修复,主要被视为暴露监测指标,但DNA加合物可能会提供有关暴露的致突变意义的更多信息。可用于测量蛋白质和DNA加合物的技术包括质谱分析法、免疫测定法、带紫外、荧光或电化学检测的高效液相色谱法、32P后标记法(仅用于DNA)和加速器质谱分析法。蛋白质加合物测量的最低灵敏度极限低于1皮摩尔加合物/克蛋白质,DNA加合物测定方法的灵敏度范围为每10^8至10^11个核苷酸中有1个加合物。所有这些技术都能够测量环境、职业和饮食中对各种基因毒性化合物的暴露情况,本综述中对此进行了举例说明。

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