Shields P G, Sugimura H, Caporaso N E, Petruzzelli S F, Bowman E D, Trump B F, Weston A, Harris C C
Laboratory of Human Carcinogenesis, National Cancer Institute, Bethesda, MD 20892.
Environ Health Perspect. 1992 Nov;98:191-4. doi: 10.1289/ehp.9298191.
Human cancer risk assessment at a genetic level involves the investigation of carcinogen metabolism and DNA adduct formation. Wide interindividual differences in metabolism result in different DNA adduct levels. For this and other reasons, many laboratories have considered DNA adducts to be a measure of the biologically effective dose of a carcinogen. Techniques for studying DNA adducts using chemically specific assays are becoming available. A modification of the 32P-postlabeling assay for polycyclic aromatic hydrocarbon DNA adducts described here provides potential improvements in quantification. DNA adducts, however, reflect only recent exposure to carcinogens; in contrast, genetic testing for metabolic capacity indicates the extent to which carcinogens can be activated and exert genotoxic effects. Such studies may reflect both separate and integrated risk factors together with DNA adduct levels. A recently described restriction fragment length polymorphism for the CYP1A1, which codes for the cytochrome P450 enzyme primarily responsible for the metabolic activation of carcinogenic polycyclic aromatic hydrocarbons, has been found to be associated with lung cancer risk in a Japanese population. In a subset of individuals enrolled in a U.S. lung cancer case-control study, no association with lung cancer was found.
在基因水平上进行人类癌症风险评估涉及对致癌物代谢和DNA加合物形成的研究。代谢过程中存在广泛的个体差异，这导致了不同的DNA加合物水平。基于这一原因及其他因素，许多实验室认为DNA加合物是衡量致癌物生物学有效剂量的指标。利用化学特异性检测方法研究DNA加合物的技术已逐渐问世。本文所述的用于多环芳烃DNA加合物的32P后标记检测法的改进，有望在定量方面取得进展。然而，DNA加合物仅反映近期对致癌物的接触情况；相比之下，对代谢能力的基因检测则表明致癌物能够被激活并产生基因毒性作用的程度。此类研究可能会将单独的和综合的风险因素与DNA加合物水平一同反映出来。最近描述的一种细胞色素P450酶（主要负责致癌多环芳烃的代谢激活）CYP1A1的限制性片段长度多态性，已被发现在日本人群中与肺癌风险相关。而在美国肺癌病例对照研究的一部分受试者中，未发现其与肺癌存在关联。
