DNA ADDUCTS IN HUMAN URINARY-BLADDER AND OTHER TISSUES
DNA ADDUCTS IN HUMAN URINARY-BLADDER AND OTHER TISSUES
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DOI：
10.2307/3431456
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发表时间：
1993-03-01
影响因子：
10.4
通讯作者：
HEWER, A
中科院分区：
文献类型：
--
作者：
PHILLIPS, DH;HEWER, A
吸烟与许多器官的癌症风险增加有关，包括膀胱癌和肺癌。烟草烟雾含有至少50种已知的化学致癌物，这些致癌物通过与细胞DNA的共价结合发挥其生物效应。检查人类DNA中是否存在核苷酸变化是监测接触遗传有毒化学物质的一种手段。从73例人膀胱活检组织中提取DNA，用P-32-后标记分析芳香/疏水加合物的存在。丁醇提取DNA酶解物的加合物回收率是核酸酶P_1消化法的3倍。在16名非吸烟者中，加合物水平在3.2-20.8/10(8)核苷酸范围内(平均9.7)。8名戒烟者的得分范围在2.6-12.3(平均7.1)之间。13名吸烟者的加合物水平在1.3到26.7加合物/10(8)核苷酸之间(平均9.5，与不吸烟者没有区别)。6个抽雪茄的人有更高的加合物水平(平均12.1，范围7.3-15.0)，但烟斗吸烟者没有(5个样本，平均8.6，范围2.9-12.7)。另外8个来自不吸烟者和17个来自吸烟者的样本被更详细地检查。尽管大多数脱氧核糖核酸结合似乎与吸烟无关，但在吸烟者中发现一个加合物的水平平均高出2倍(p<；0.005，单尾t检验)。对呼吸道组织的研究表明，DNA加合物水平与烟草烟雾暴露之间存在相关性。到目前为止，关于吸烟对外周血细胞中加合物的影响的证据是模棱两可的；一些研究表明了显著的影响，而另一些研究则没有。吸烟对血细胞加合物形成的影响可能较弱，而其他不明原因的暴露影响较大。
Tobacco smoking is associated with an increased risk of cancer in a number of organs, including bladder and lung. Tobacco smoke contains at least 50 known chemical carcinogens that exert their biological effects through their covalent binding to cellular DNA. Examining human DNA for the presence of altered nucleotides is a means of monitoring exposure to genotoxic chemicals. DNA isolated from 73 human bladder biopsies has been analyzed by P-32-postlabeling for the presence of aromatic/hydrophobic adducts. Butanol extraction of DNA digests resulted in up to a 3-fold greater recovery of adducts than nuclease P1 digestion. Among 16 nonsmokers, adduct levels were in the range 3.2-20.8/10(8) nucleotides (mean 9.7). Eight ex-smokers had values in the range 2.6-12.3 (mean 7.1). Thirteen smokers had adduct levels between 1.3 and 26.7 adducts/10(8) nucleotides (mean 9.5, not different from nonsmokers). Six cigar smokers had higher levels of adducts (mean 12.1, range 7.3-15.0), but pipe smokers did not (five samples, mean 8.6, range 2.9-12.7). A further 8 samples from nonsmokers and 17 from smokers were examined in more detail. Although most of the DNA binding appears not to be smoking related, the levels of one adduct were found to be on average 2-fold higher in smokers (p < 0.005, one-tailed t test). Studies on tissues of the respiratory tract demonstrate a correlation between DNA adduct levels and exposure to tobacco smoke. Evidence to date on the influence of smoking on adducts in peripheral blood cells is equivocal; some studies demonstrate a significant effect, whereas others do not. It is probable that the effect of smoking on adduct formation on blood cells is a weak one and that other undetermined exposures have greater influence.