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支气管活检中的DNA加合物

DNA adducts in bronchial biopsies.

作者信息

Dunn B P, Vedal S, San R H, Kwan W F, Nelems B, Enarson D A, Stich H F

机构信息

British Columbia Cancer Research Centre, Vancouver, Canada.

出版信息

Int J Cancer. 1991 Jun 19;48(4):485-92. doi: 10.1002/ijc.2910480403.

Abstract

To investigate the feasibility of measuring DNA-carcinogen adducts in the lungs of non-surgical patients, endobronchial biopsies were obtained from 78 patients undergoing routine diagnostic bronchoscopy. Lung cancer was present in 37 (47%) of the patients. DNA was isolated from the tissues and analyzed by HPLC- or nuclease-PI-enriched 32P-postlabelling, using procedures selective for aromatic adducts. Chromatograms from all 28 current smokers showed a distinctive diagonal adduct zone which was present in only 24 of 40 ex-smokers and 4 of 10 lifetime non-smokers. Adduct levels and chromatographic patterns were similar in bronchial tissue from different lobes of the lung, in bronchial and alveolar tissue, and in tumor and non-tumor bronchial tissue taken from the same subject. Bronchial DNA adduct levels were strongly associated with cigarette smoking status and dropped rapidly after smoking ceased. Higher levels of DNA adducts seen in the lung-cancer patients were mainly due to cigarette smoking. Frequent alcohol intake was the only dietary factor associated with higher levels of bronchial DNA adducts. We conclude that the level of bronchial DNA adducts is strongly associated with cigarette-smoking history and with alcohol intake, but is not associated with lung cancer independently from its relation to smoking. The results indicate the feasibility of using 32P-postlabelling to detect and quantitate genetic damage in bronchial biopsy specimens.

摘要

为研究在非手术患者肺部测量DNA - 致癌物加合物的可行性,从78例接受常规诊断性支气管镜检查的患者中获取了支气管活检组织。37例(47%)患者患有肺癌。从组织中分离出DNA,并采用对芳香族加合物有选择性的方法,通过高效液相色谱法或核酸酶 - PI富集的32P后标记法进行分析。所有28例当前吸烟者的色谱图均显示出一个独特的对角加合物区,而在40例既往吸烟者中只有24例出现该区域,在10例终生不吸烟者中只有4例出现。加合物水平和色谱模式在肺不同叶的支气管组织、支气管和肺泡组织以及同一受试者的肿瘤和非肿瘤支气管组织中相似。支气管DNA加合物水平与吸烟状况密切相关,戒烟后迅速下降。肺癌患者中较高水平的DNA加合物主要归因于吸烟。频繁饮酒是与较高水平支气管DNA加合物相关的唯一饮食因素。我们得出结论,支气管DNA加合物水平与吸烟史和饮酒密切相关,但与肺癌的关系独立于其与吸烟的关系。结果表明,使用32P后标记法检测和定量支气管活检标本中的遗传损伤是可行的。

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