Covalent DNA damage in tissues of cigarette smokers as determined by 32P-postlabeling assay.
Covalent DNA damage in tissues of cigarette smokers as determined by 32P-postlabeling assay.
复制标题
通过 32P 标记后测定确定吸烟者组织中的共价 DNA 损伤。
DOI：
10.1093/jnci/81.5.341
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发表时间：
1989
期刊：
影响因子：
--
通讯作者：
Randerath,K
中科院分区：
文献类型：
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作者：
Randerath,E;Miller,RH;Mittal,D;Avitts,TA;Dunsford,HA;Randerath,K
化学致癌物或其代谢产物与DNA反应形成的共价DNA加成产物（加合物）在化学致癌作用的启动中起着关键作用，并可作为环境致癌物暴露的分子标记物和剂量计。采用高灵敏度的32 P-后标记DNA加合物分析法，研究了香烟烟雾引起的吸烟者组织DNA损伤。大量的特征性吸烟诱导的，大概是芳香族DNA加合物被发现发生在剂量和时间依赖性的方式在吸烟者的肺，支气管和喉与这些器官的癌症和戒烟后才缓慢下降。低水平的加合物似乎持续了长达14年的肺中的吸烟者与高以前的曝光。这些结果证实了流行病学研究的数据，即吸烟者患肺癌的风险和死亡率随着吸烟的强度和持续时间的增加而增加，只有在戒烟后才缓慢下降。尸检样本的组织分布研究显示，在肾脏、膀胱、食道、心脏、升主动脉和肝脏中也存在吸烟相关的DNA损伤。肺和心脏中发现了最广泛的DNA损伤，即，1个芳香加合物。我们的研究结果表明，吸烟诱导的DNA加合物的形成与靶器官中的癌症有因果关系。[J Natl Cancer Inst 81：341-347，1989]
Covalent DNA addition products (adducts) formed by the reaction of chemical carcinogens or their metabolites with DNA are critically involved in the initiation of chemical carcinogenesis and may serve as molecular markers and dosimeters for environmental carcinogen exposures. Using a highly sensitive32P-postlabeling assay for DNA adduct analysis, we studied DNA damage elicited by cigarette smoke in tissues of smokers. A multitude of characteristic smoking-induced, presumably aromatic DNA adducts were found to occur in a dose-and time-dependent manner in the lung, bronchus, and larynx of smokers with cancer of these organs and to decline only slowly after cessation of smoking. Low levels of adducts appeared to persist for up to 14 years in the lungs of exsmokers with high previous exposures. These results corroborate data of epidemiological studies showing that the lung cancer risk and mortality of smokers increase with the intensity and duration of smoking and decline only slowly after cessation of smoking. Tissue distribution studies in autopsy samples revealed the presence of smoking-associated DNA lesions also in the kidney, bladder, esophagus, heart, ascending aorta, and liver. The most extensive DNA damage was found in lung and heart, i.e., 1 aromatic adduct in about 107DNA nucleotides. Our results suggest that cigarette smoking-induced DNA adduct formation is causally related to cancer in the target organs. [J Natl Cancer Inst 81:341–347, 1989]