肺癌和肺癌前病变组织中多环芳烃-DNA加合物的检测

Detection of PAHs-DNA adduct in human lung precancerous lesions and lung cancer tissues

目的苯并（a）芘等多环芳烃（PAHS）的代谢产物作用于DNA可形成多环芳烃-DNA（PAHS—DNA）加合物，由此导致细胞的恶变和肿瘤的发生。本研究是为了探明多环芳烃-DNA加合物在人类肺癌发生中的作用。方法通过免疫学方法检测108例肺癌患者手术标本、41例支气管黏膜上皮不典型增生组织及41例正常肺组织中该加合物的含量，并检测体外人气管上皮细胞癌变过程中多环芳烃-DNA加合物的动态变化。结果14．6％（6／41）的正常肺组织中可检测到多环芳烃-DNA加合物；70．7％（29／41）的支气管黏膜上皮不典型增生组织和84．3％（91／108）的肺癌组织中可检出多环芳烃-DNA加合物；组间差异有显著性意义，P〈0．001；且随着肺组织癌变过程的变化，多环芳烃-DNA加合物的检出率呈逐渐增高的趋势，P〈0．001。吸烟者该加合物检出率高于非吸烟者。苯并（a）芘的活性代谢产物BPDE可诱导人气管上皮细胞发生转化，多环芳烃-DNA加合物与细胞的转化、癌变过程相一致。结论多环芳烃-DNA加合物与肺的癌变过程密切相关，它是化学致癌过程中的一个早期可检测的生物标记物。

Objective The metabolic of polycyclic aromatic hydrocarbons （PAHs）,including benzo[a]pyrene [B（a）P],can induce PAHs-DNA adduct and carcinogenesis. We conducted this study to investigate the role of PAHs-DNA adduct in the development of human lung cancer. Methods Immunohistochemistry staining was used to detect the PAHs-DNA adduct in 108 cases of lung cancer tissues, 41cases of bronchus epithelium tissues and 41 cases of normal lung tissues. We also detected the PAHs-DNA adduct during the process of carcinogenesis of human bronchial epithelial cells induced by the metabolic of B（a）P （BPDE） in vitro. Results The expression rate of PAHs-DNA adduct was 14.6%（6/41） in normal lung tissues, 70.7%（29/41）in atypical hyperplasia of bronchus epithelium tissues, and 84.3%（91/108） in lung cancer tissues,the difference among them was high significant, P〈0. 001, and there was a trend for expression of PAHs-DNA adduct from normal lungs to atypical hyperplasia of bronchus epithelium, and to lung cancer, P〈0. 001. The expression of PAHs-DNA adduct were higher in the smokers than that of non-smokers. PAHs-DNA adduct were detected simultaneously in BPDE transformed human bronchial epithelium cells. Conclusion PAHs-DNA adduct is associated with lung carcinogenesis, smoking exposure can cause PAHs-DNA adduct, and this PAHs-DNA adduct is an early detectable biomarker for the study of chemical carcinogenesis.