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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.

DOI:10.1002/ijc.2910480403
PMID:2045196
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。

相似文献

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DNA adducts in bronchial biopsies.支气管活检中的DNA加合物
Int J Cancer. 1991 Jun 19;48(4):485-92. doi: 10.1002/ijc.2910480403.
2
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Carcinogenesis. 2004 Jul;25(7):1201-9. doi: 10.1093/carcin/bgh131. Epub 2004 Mar 4.
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Determination of smoking-related DNA adducts in lung-cancer and non-cancer patients.肺癌患者和非癌症患者中吸烟相关DNA加合物的测定。
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Analysis of DNA adducts in smokers' lung and urothelium by 32P-postlabelling: metabolic phenotype dependence and comparisons with other exposure markers.用³²P后标记法分析吸烟者肺组织和尿路上皮中的DNA加合物:代谢表型依赖性及与其他暴露标志物的比较
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Smoking-associated bulky DNA adducts in bronchial tissue related to CYP1A1 MspI and GSTM1 genotypes in lung patients.肺部疾病患者支气管组织中与吸烟相关的大体积DNA加合物与CYP1A1 MspI和GSTM1基因型的关系。
Carcinogenesis. 1998 May;19(5):841-6. doi: 10.1093/carcin/19.5.841.
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Influence of cigarette smoking on the levels of DNA adducts in human bronchial epithelium and white blood cells.吸烟对人支气管上皮细胞和白细胞中DNA加合物水平的影响。
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Lung DNA adducts detected in human smokers are unrelated to typical polyaromatic carcinogens.在人类吸烟者中检测到的肺部DNA加合物与典型的多环芳烃致癌物无关。
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Comparison of multiple DNA adduct types in tumor adjacent human lung tissue: effect of cigarette smoking.肿瘤旁人类肺组织中多种DNA加合物类型的比较:吸烟的影响
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Polycyclic aromatic hydrocarbon-DNA adducts in lung tissue from lung cancer patients.肺癌患者肺组织中的多环芳烃-DNA加合物
Carcinogenesis. 1990 Sep;11(9):1677-81. doi: 10.1093/carcin/11.9.1677.

引用本文的文献

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DNA adducts in human tissues: biomarkers of exposure to carcinogens in tobacco smoke.人体组织中的DNA加合物:接触烟草烟雾中致癌物的生物标志物。
Environ Health Perspect. 1996 May;104 Suppl 3(Suppl 3):453-8. doi: 10.1289/ehp.96104s3453.
2
Cigarette smoking and cervical cancer.吸烟与宫颈癌
BMJ. 1993 Aug 7;307(6900):384. doi: 10.1136/bmj.307.6900.384-b.
3
Significance of DNA adduct studies in animal models for cancer molecular dosimetry and risk assessment.DNA加合物研究在癌症分子剂量测定和风险评估动物模型中的意义。
Environ Health Perspect. 1993 Mar;99:5-10. doi: 10.1289/ehp.93995.
4
DNA adducts in human urinary bladder and other tissues.人类膀胱及其他组织中的DNA加合物。
Environ Health Perspect. 1993 Mar;99:45-9. doi: 10.1289/ehp.939945.
5
Biphasic removal of DNA adducts in a repetitive DNA sequence after dietary administration of 2-acetylaminofluorene.给予2-乙酰氨基芴后,重复DNA序列中DNA加合物的双相清除
Environ Health Perspect. 1993 Mar;99:273-5. doi: 10.1289/ehp.9399273.
6
Damage to DNA in cervical epithelium related to smoking tobacco.吸烟与宫颈上皮细胞中的DNA损伤有关。
BMJ. 1993 May 29;306(6890):1444-8. doi: 10.1136/bmj.306.6890.1444.
7
Detection of DNA single-strand breaks in lymphocytes of smokers.
Int Arch Occup Environ Health. 1993;65(2):83-8. doi: 10.1007/BF00405724.
8
Determination of DNA single-strand breaks in lymphocytes of smokers and nonsmokers exposed to environmental tobacco smoke using the nick translation assay.
Clin Investig. 1994 Nov;72(11):930-6. doi: 10.1007/BF00190755.
9
The human glutathione S-transferase supergene family, its polymorphism, and its effects on susceptibility to lung cancer.人类谷胱甘肽S-转移酶超基因家族、其多态性及其对肺癌易感性的影响。
Environ Health Perspect. 1992 Nov;98:87-94. doi: 10.1289/ehp.929887.
10
Polycyclic aromatic hydrocarbon-DNA adducts and the CYP1A1 restriction fragment length polymorphism.多环芳烃-DNA加合物与CYP1A1限制性片段长度多态性
Environ Health Perspect. 1992 Nov;98:191-4. doi: 10.1289/ehp.9298191.