Poirier M C, Weston A
Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, Bethesda, Maryland 20892, USA.
Environ Health Perspect. 1996 Oct;104 Suppl 5(Suppl 5):883-93. doi: 10.1289/ehp.96104s5883.
Human DNA adduct formation (covalent modification of DNA with chemical carcinogens) is a promising biomarker for elucidating the molecular epidemiology of cancer. Classes of compounds for which human DNA adducts have been observed include polycyclic aromatic hydrocarbons (PAHs), nitrosamines, mycotoxins, aromatic amines, heterocyclic amines, ultraviolet light, and alkylating cancer chemotherapeutic agents. Most human DNA adduct exposure monitoring has been performed with either 32P-postlabeling or immunoassays, neither of which is able to chemically characterize specific DNA adducts. Recently developed combinations of methods with chemical and physical end points have allowed identification of specific adducts in human tissues. Studies are presented that demonstrate that high ambient levels of benzo[a]pyrene are associated with high levels of DNA adducts in human blood cell DNA and that the same DNA adduct levels drop when the ambient PAH levels decrease significantly. DNA adduct dosimetry, which has been achieved with some dietary carcinogens and cancer chemotherapeutic agents, is described, as well as studies correlating DNA adducts with other biomarkers. It is likely that some toxic, noncarcinogenic compounds may have genotoxic effects, including oxidative damage, and that adverse health outcomes other than cancer may be correlated with DNA adduct formation. The studies presented here may serve as useful prototypes for exploration of other toxicological end points.
人类DNA加合物的形成（DNA与化学致癌物的共价修饰）是阐明癌症分子流行病学的一个有前景的生物标志物。已观察到人类DNA加合物的化合物类别包括多环芳烃（PAHs）、亚硝胺、霉菌毒素、芳香胺、杂环胺、紫外线和烷基化癌症化疗药物。大多数人类DNA加合物暴露监测是通过32P后标记法或免疫测定法进行的，这两种方法都无法对特定的DNA加合物进行化学表征。最近开发的结合化学和物理终点的方法组合使得在人体组织中鉴定特定加合物成为可能。所呈现的研究表明，环境中高浓度的苯并[a]芘与人类血细胞DNA中的高浓度DNA加合物相关，并且当环境中PAH水平显著降低时，相同的DNA加合物水平也会下降。描述了用一些膳食致癌物和癌症化疗药物实现的DNA加合物剂量测定法，以及将DNA加合物与其他生物标志物相关联的研究。一些有毒的非致癌化合物可能具有遗传毒性作用，包括氧化损伤，并且除癌症之外的不良健康结果可能与DNA加合物的形成相关。这里呈现的研究可能作为探索其他毒理学终点有用的范例。
