Perera F, Mayer J, Jaretzki A, Hearne S, Brenner D, Young T L, Fischman H K, Grimes M, Grantham S, Tang M X
Division of Environmental Sciences, Columbia University School of Public Health, New York, New York 10032.
Cancer Res. 1989 Aug 15;49(16):4446-51.
In a molecular epidemiological study of lung cancer cases (n = 81) and noncancer controls (n = 67), polycyclic aromatic hydrocarbon (PAH)-DNA adducts were evaluated in peripheral blood leukocytes from all subjects and in a smaller number of lung tissue specimens collected prior to or at surgery. Sister chromatid exchanges (SCE) in lymphocytes were also studied in a subset of cases and controls. Questionnaire, medical record, or tumor registry data provided a family history of cancer, as well as information on cigarette smoking, dietary and occupational exposure to PAHs, and other factors related to SCEs. In both cases and controls PAH-DNA adducts in leukocytes measured by an enzyme-linked immunosorbent assay were not significantly related to age, sex, ethnicity, amount of cigarette smoking, passive smoking, dietary charcoal, or caffeine consumption. Nor did family history of cancer or histological type of cancer significantly affect adduct levels. However, when subjects were stratified by smoking status (current, former, and nonsmoker), lung cancer cases who were current smokers had significantly higher levels of covalent adducts than current smoker controls. A seasonal variation was observed in PAH-DNA binding, with a peak in adduct levels during July-October. This peak corresponds to that seen in a prior study of aryl hydrocarbon hydroxylase inducibility by other investigators. The finding of significant levels of PAH-DNA adducts in former smokers and non-smokers supports an earlier observation that this marker is not smoking specific but reflects a pervasive and variable "background" exposure to PAH. These results are consistent with a genetically determined enhancement of PAH-DNA adduct formation in leukocytes of lung cancer cases which is evident in current smokers. The results in lung tissue are limited by the small number of samples. Adduct levels were not significantly increased in lung tissue of smokers compared with nonsmokers. An inverse linear correlation was seen between adduct values in lung tissue and age of the donors. SCEs were significantly related to pack years of smoking. However, there was no difference in the frequency of SCE between cases and controls; nor were SCE and DNA adducts significantly correlated in this small sample.
在一项针对肺癌病例（n = 81）和非癌症对照者（n = 67）的分子流行病学研究中，对所有受试者外周血白细胞以及少量在手术前或手术时采集的肺组织标本中的多环芳烃（PAH）-DNA加合物进行了评估。还对一部分病例和对照者的淋巴细胞中的姐妹染色单体交换（SCE）进行了研究。通过问卷调查、病历或肿瘤登记数据获取癌症家族史，以及关于吸烟、饮食和职业性接触PAH的信息，还有其他与SCE相关的因素。在病例组和对照组中，通过酶联免疫吸附测定法测得的白细胞中PAH-DNA加合物与年龄、性别、种族、吸烟量、被动吸烟、饮食中木炭或咖啡因摄入量均无显著相关性。癌症家族史或癌症组织学类型也未对加合物水平产生显著影响。然而，当按吸烟状况（当前吸烟者、既往吸烟者和不吸烟者）对受试者进行分层时，当前吸烟者中的肺癌病例的共价加合物水平显著高于当前吸烟者对照。观察到PAH-DNA结合存在季节性变化，加合物水平在7月至10月达到峰值。该峰值与其他研究者先前关于芳烃羟化酶诱导性的研究中观察到的峰值一致。在既往吸烟者和不吸烟者中发现显著水平的PAH-DNA加合物，这支持了早期的一项观察结果，即该标志物并非吸烟特异性的，而是反映了普遍存在且变化的PAH“背景”暴露。这些结果与肺癌病例白细胞中PAH-DNA加合物形成的遗传决定增强一致，这在当前吸烟者中很明显。肺组织的结果因样本数量少而受到限制。与不吸烟者相比，吸烟者肺组织中的加合物水平没有显著升高。肺组织中的加合物值与供体年龄呈负线性相关。SCE与吸烟包年数显著相关。然而，病例组和对照组之间的SCE频率没有差异；在这个小样本中，SCE与DNA加合物也没有显著相关性。
