Bartsch H, Castegnaro M, Rojas M, Camus A M, Alexandrov K, Lang M
International Agency for Research on Cancer, Lyon, France.
Toxicol Lett. 1992 Dec;64-65 Spec No:477-83. doi: 10.1016/0378-4274(92)90222-6.
Cigarette smoking is the strongest risk factor for lung cancer (LC), but genetically determined variations in pulmonary metabolism of tobacco-derived carcinogens may affect individual risk. Results from a case-control study on LC patients demonstrated the pronounced effect of tobacco smoke on pulmonary xenobiotic metabolism and prooxidant state, and suggested the existence of a metabolic phenotype at higher risk for tobacco-associated LC: LC patients who were recent smokers had significantly induced BP-3-hydroxylase (AHH) and ethoxycoumarin O-deethylase (ECDE) activities in lung parenchyma, when compared with smoking non-cancer patients. In recent smokers, lung AHH activity was positively correlated with the level of tobacco smoke-derived DNA adducts as determined by 32P-postlabelling. Pulmonary AHH activity also showed a good correlation with the intensity of immunohistochemical staining for cyt. P4501A by a monoclonal Ab in lung tissue sections: smoking and peripheral type of lung cancers were positively related to high levels of this cyt. P450 species, probably reflecting high rates of induction. These results suggest that high pulmonary CYP1A1 expression (controlling in part carcinogen DNA-adduct formation) in tobacco smokers, appears to be associated with LC risk. High risk subjects may thus be identifiable through genotyping assays for CYP1A1 polymorphism.
吸烟是肺癌（LC）最强的风险因素，但烟草衍生致癌物肺部代谢的基因决定变异可能会影响个体风险。一项针对LC患者的病例对照研究结果表明，烟草烟雾对肺部异生物质代谢和促氧化状态有显著影响，并提示存在一种与烟草相关LC风险较高的代谢表型：与吸烟的非癌症患者相比，近期吸烟者的LC患者肺实质中苯并芘-3-羟化酶（AHH）和乙氧香豆素O-脱乙基酶（ECDE）活性显著升高。在近期吸烟者中，肺AHH活性与通过32P后标记法测定的烟草烟雾衍生DNA加合物水平呈正相关。肺AHH活性也与肺组织切片中细胞色素P4501A单克隆抗体免疫组化染色强度有良好的相关性：吸烟和周围型肺癌与该细胞色素P450物种的高水平呈正相关，这可能反映了高诱导率。这些结果表明，吸烟者肺部CYP1A1高表达（部分控制致癌物DNA加合物形成）似乎与LC风险相关。因此，通过CYP1A1多态性基因分型检测可能识别出高风险个体。
