Phillips D H, Schoket B, Hewer A, Bailey E, Kostic S, Vincze I
Chester Beatty Laboratories, Institute of Cancer Research, London, UK.
Int J Cancer. 1990 Oct 15;46(4):569-75. doi: 10.1002/ijc.2910460403.
The presence of carcinogen-DNA adducts in human tissues is evidence of exposure to carcinogens and may be an indicator of cancer risk. DNA was isolated from non-tumorous bronchial tissue of 37 cigarette smokers, 8 former smokers and 8 non-smokers and analyzed for the presence of aromatic and/or hydrophobic DNA adducts in the 32P-post-labelling assay. Adducts were detected as bands of radioactive material when 5'-32P-labelled deoxyribonucleoside 3',5'-bisphosphates were chromatographed on polyethyleneimine-cellulose tlc plates, and the patterns indicated the formation of adducts by a large number of compounds. Adduct levels detected in DNA from non-smokers, former smokers and current smokers were 3.45 +/- 1.62, 3.93 +/- 1.92 and 5.53 +/- 2.13 adducts/10(8) nucleotides, respectively. The differences in adduct levels between smokers and former and non-smokers were statistically significant (p less than 0.01); and among the smokers, significant correlations were found between adduct levels and both daily cigarette consumption and total cigarette consumption (daily consumption X number of years smoked). DNA was also isolated from the peripheral-blood leukocytes of 31 heavy smokers (greater than 20 cigarettes/day) and 20 non-smokers and analyzed by 32P-post-labelling. Adduct levels in the smokers' samples were not significantly different from levels in the non-smokers' samples (2.53 +/- 1.31 and 2.12 +/- 1.44 adducts/10(8) nucleotides, respectively). Thus, evidence for carcinogen exposure was found in human bronchial epithelium, a target tissue for tobacco-induced tumour formation, but not in peripheral-blood cells, indicating possible limitations in the use of the latter as a surrogate, non-target tissue source of DNA for monitoring human exposure to inhaled carcinogens.
人体组织中致癌物 - DNA加合物的存在是接触致癌物的证据,并且可能是癌症风险的一个指标。从37名吸烟者、8名既往吸烟者和8名不吸烟者的非肿瘤性支气管组织中分离出DNA,并通过32P后标记分析法分析其中芳香族和/或疏水性DNA加合物的存在情况。当5'-32P标记的脱氧核糖核苷3',5'-二磷酸在聚乙烯亚胺 - 纤维素薄层层析板上进行色谱分析时,加合物被检测为放射性物质条带,其图谱表明有大量化合物形成了加合物。在不吸烟者、既往吸烟者和当前吸烟者的DNA中检测到的加合物水平分别为3.45±1.62、3.93±1.92和5.53±2.13个加合物/10(8)个核苷酸。吸烟者与既往吸烟者和不吸烟者之间加合物水平的差异具有统计学意义(p<0.01);在吸烟者中,加合物水平与每日吸烟量和总吸烟量(每日吸烟量×吸烟年数)之间均存在显著相关性。还从31名重度吸烟者(每天吸烟超过20支)和20名不吸烟者的外周血白细胞中分离出DNA,并通过32P后标记法进行分析。吸烟者样本中的加合物水平与不吸烟者样本中的水平无显著差异(分别为2.53±1.31和2.12±1.44个加合物/10(8)个核苷酸)。因此,在人体支气管上皮(烟草诱导肿瘤形成的靶组织)中发现了致癌物暴露的证据,但在外周血细胞中未发现,这表明将外周血细胞作为监测人体吸入致癌物暴露的替代非靶组织DNA来源可能存在局限性。