Wiencke J K, Kelsey K T, Varkonyi A, Semey K, Wain J C, Mark E, Christiani D C
Department of Epidemiology and Biostatistics, School of Medicine, University of California, San Francisco 94143-0560, USA.
Cancer Res. 1995 Nov 1;55(21):4910-4.
The formation of carcinogen-DNA adducts within the respiratory epithelium is thought to be a critical factor in the induction of lung cancer from tobacco smoke. A reliable surrogate measure of carcinogen damage to the lung would be of great value in molecular epidemiological studies of cancer risk. The validity of measurements of DNA adducts formed from hydrophobic aromatic hydrocarbons in peripheral blood mononuclear cells (MNCs) was investigated by comparing the levels of aromatic DNA adducts detected in lung tissue from 31 lung cancer patients with those detected in MNCs from the same individuals using the 32P-postlabeling assay. The associations of smoking history and intake of dietary antioxidants with adduct levels also were assessed. Tissue-specific, as well as common DNA adducts were detected in lung and blood; total MNC adduct levels were highly correlated with total lung adducts. After smoking cessation, adduct levels appeared to decay in both tissues at similar rates. Multivariate analyses (Poisson regression modeling) indicated that dietary antioxidant intake (carotenoids, vitamin A, and retinol) modified the levels of aromatic DNA adducts in both the lungs and blood. Of all models tested, the optimal one for predicting lung adduct levels included the measure of blood MNC adduct levels only. Therefore, blood MNCs are a valid surrogate tissue for estimating the burden of DNA adducts in respiratory tissue in molecular epidemiological studies.
呼吸道上皮内致癌物 - DNA加合物的形成被认为是吸烟诱发肺癌的关键因素。在癌症风险的分子流行病学研究中，一种可靠的衡量致癌物对肺部损害的替代指标将具有重要价值。通过使用32P后标记分析法，比较31名肺癌患者肺组织中检测到的芳香族DNA加合物水平与同一患者外周血单核细胞（MNC）中检测到的水平，研究了外周血单核细胞中由疏水性芳香烃形成的DNA加合物测量的有效性。还评估了吸烟史和膳食抗氧化剂摄入量与加合物水平的关联。在肺和血液中检测到了组织特异性以及常见的DNA加合物；外周血单核细胞加合物总水平与肺加合物总水平高度相关。戒烟后，两个组织中的加合物水平似乎以相似的速率下降。多变量分析（泊松回归模型）表明，膳食抗氧化剂摄入量（类胡萝卜素、维生素A和视黄醇）会改变肺和血液中芳香族DNA加合物的水平。在所有测试模型中，预测肺加合物水平的最佳模型仅包括外周血单核细胞加合物水平的测量值。因此，在外周血单核细胞是分子流行病学研究中估计呼吸道组织中DNA加合物负担的有效替代组织。
