Santella Regina M, Gammon Marilie, Terry MaryBeth, Senie Ruby, Shen Jing, Kennedy David, Agrawal Meenakshi, Faraglia Beatrice, Zhang FangFang
Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, 701 West 168th St., New York, NY 10032, USA.
Mutat Res. 2005 Dec 30;592(1-2):29-35. doi: 10.1016/j.mrfmmm.2005.06.001. Epub 2005 Jul 14.
It is well established that the initiating event in chemical carcinogenesis is the binding of reactive carcinogens to DNA. Thus, a number of analytic methods have been developed for determining levels of carcinogen-DNA adducts in humans as a marker of individual exposure and, potentially, of risk for cancer development. We have developed monoclonal and polyclonal antibodies to carcinogen-DNA adducts and highly sensitive ELISA and immunohistochemical assays for determining levels of adducts in human tissues. These methods have been combined with genotyping and phenotyping methods for DNA repair to study gene-environment interactions in cancer risk. Recent studies on breast cancer have utilized two large biorepositories. The first is blood and tumor tissues collected as part of the Long Island Breast Cancer Study Project, a population-based case-control study of environmental risk factors. The second is the Metropolitan New York Registry of Breast Cancer Families, one of six sites funded by the National Cancer Institute as a part of the Breast Cooperative Family Registry (CFR). Analysis of samples from these two studies have demonstrated the utility of measurement of DNA adducts as biomarkers of exposure and that DNA repair capacity, measured by genotyping or phenotyping, can influence risk.
化学致癌作用中的起始事件是反应性致癌物与DNA的结合，这一点已得到充分证实。因此，已经开发了多种分析方法来测定人体中致癌物-DNA加合物的水平，以此作为个体暴露的标志物，并潜在地作为癌症发生风险的标志物。我们已经开发了针对致癌物-DNA加合物的单克隆抗体和多克隆抗体，以及用于测定人体组织中加合物水平的高度灵敏的酶联免疫吸附测定法（ELISA）和免疫组织化学测定法。这些方法已与DNA修复的基因分型和表型分型方法相结合，以研究癌症风险中的基因-环境相互作用。最近关于乳腺癌的研究利用了两个大型生物样本库。第一个是作为长岛乳腺癌研究项目的一部分收集的血液和肿瘤组织，该项目是一项基于人群的环境风险因素病例对照研究。第二个是纽约市大都会乳腺癌家族登记处，它是美国国家癌症研究所资助的六个地点之一，作为乳腺癌合作家族登记处（CFR）的一部分。对来自这两项研究的样本进行分析表明，测量DNA加合物作为暴露生物标志物具有实用性，并且通过基因分型或表型分型测量的DNA修复能力会影响风险。
