【摘要】 目的研究外源性化学物代谢酶和DNA损伤修复酶基因多态性与焦炉作业工人外周血淋巴细胞DNA损伤易感性的关系。方法选取144名焦炉作业工人(暴露组)和50名医务人员(对照组)作为研究对象,测定其尿中1羟基芘浓度来反映多环芳烃暴露内剂量,用碱性彗星试验评价个体外周血淋巴细胞DNA损伤,分析细胞色素P4501A1、细胞色素P4502E1、谷胱甘肽S转移酶P1(GSTP1)、还原型辅酶2醌氧化还原酶、环氧化物水化酶和XRCC1基因的多态性,以及不同基因型与DNA损伤的关系。结果暴露组尿中1羟基芘浓度为11.8μmol/mol肌酐、彗星尾矩为3.2,均高于对照组(尿中1羟基芘浓度为0.7μmol/mol肌酐、彗星尾矩为1.1);暴露组中XRCC1Arg280His位点变异基因型个体的彗星尾矩(5.6)显著高于野生型个体(2.8)。以1.74为界值,将全部研究对象的彗星尾矩转化为分类变量后的回归分析结果表明,XRCC1Arg280His位点变异基因型个体发生DNA损伤的危险度显著高于野生基因型个体;GSTP1Ile104Val位点变异基因型个体发生DNA损伤的危险度高于野生基因型个体,但差异无统计学意义。结论XRCC1280His和GSTP1104Val等位基因可增加职业性多环芳烃暴露导致的外周血淋巴细胞DNA损伤水平。更多还原

【Abstract】 Objective To investigate the association of polymorphisms of metabolic and DNA repair enzyme genes and DNA damage in peripheral blood lymphocytes in coke-oven workers.Methods One hundred and fourty-four coke-oven workers and 50 controls were recruited in this study. Urinary 1-hydroxypyrene (1-OHP) levels were measured as the internal dose of polycyclic aromatic hydrocarbons exposure. DNA damage was detected by alkaline comet assay, and the value of 1.74 was used as the cut-off value to determine whether the individual’s DNA damage was positive.The genotypes of CYP1A1, CYP2E1, GSTP1, NQO1, mEH and XRCC1 were determined by PCR-based methods. With adjustment for urinary 1-OHP, age, sex, multiple analysis of covariance was used to study the association between genotypes and the ln-transformed olive TM and multiple logistic regression was used to calculate the adjusted OR and the 95%CI for the risk of DNA damage.Results In 144 coke-oven workers, with adjustment for urinary 1-OHP, coking history and sex,the olive TM was significantly higher with XRCC1 280His allele than those with Arg allele (5.6 vs. 2.8,P<0.01). The subjects with XRCC1 280His allele also have significantly higher risk for DNA damage than subjects with Arg allele (adjusted OR=2.66, 95%CI=1.00-7.14,P=0.05) and the subjects with GSTP1 104Val allele have higher risk for DNA damage than subjects with Ile allele (adjusted OR=1.90, 95%CI=0.94-3.85,P=0.07).Conclusion XRCC1 and GSTP1 polymorphisms might influence the susceptibility of DNA damage in occupational PAH-exposed coke-oven workers.更多还原