焦炉作业工人外周血淋巴细胞染色体损伤的遗传易感性研究  

A study on the inherited susceptibility of chromosomal damage in peripheral blood lymphocytes among coke oven workers

作　　者：冷曙光[1] 郑玉新[1] 潘祖飞[2] 牛勇[1] 戴宇飞[1] 王雅文[1] 张文众[1] 肖军[2] 王忠旭[3] 李涛[1] 何凤生[1] 

机构地区：[1]中国疾病预防控制中心职业卫生与中毒控制所,北京100050 [2]本溪钢铁集团有限责任公司劳动卫生研究所 [3]鞍山钢铁集团公司劳动卫生研究所

出　　处：《中华预防医学杂志》2004年第2期94-98,共5页Chinese Journal of Preventive Medicine

基　　金：国家自然科学基金资助项目 ( 3 9970 63 3 ) ;国家重点基础研究规划项目资助 ( 2 0 0 2CB5 12 90 3 )

摘　　要：目的　研究外源性化学物代谢酶基因多态性与焦炉作业工人外周血淋巴细胞染色体损伤的关系。方法　选取 14 9名焦炉作业工人和 2 4名非职业多环芳烃 (PAH)暴露人员作为研究对象 ,测定其尿中 1 羟基芘浓度来反映PAH暴露的内剂量 ;对照组的外周血淋巴细胞微核水平的上 4分位数 (6‰ )作为判断个体染色体损伤阳性的界值 ;分析CYP1A1、GSTM1、GSTT1、GSTP1、CYP2E1、NQO1、NAT2和mEH基因的多态性 ;使用多元logistic回归方程校正职业暴露情况、年龄、性别、吸烟和饮酒状况因素 ,计算不同基因型工人发生染色体损伤阳性的OR值 ,并探讨基因间的交互作用。结果　调整了 173名研究对象的职业暴露、年龄、性别、吸烟和饮酒状况后 ,GSTM 1缺失基因型个体染色体损伤危险度显著性增加 (调整OR =2 0 1,95 %CI =1 0 3～ 3 91) ;与NQO1基因P187S位点野生型纯合子个体比较 ,变异型纯合子个体染色体损伤危险度显著性增加 (调整OR =3 18,95 %CI=1 18～ 8 6 2 ) ;与mEH基因H113Y位点野生型纯合子个体比较 ,变异型纯合子个体染色体损伤危险度显著性降低 (调整OR =0 4 0 ,95 %CI =0 19～ 0 88) ;未发现其他基因的遗传变异与研究对象外周血淋巴细胞染色体损伤危险度的显著关联。此外 ,还发现GSTM1、NQO1基因P187S位点和mEH基?Objective To investigate the association between polymorphisms of metabolic enzyme genes and chromosomal damage risk in peripheral blood lymphocytes among coke oven workers Methods One hundred and fourty nine coke oven workers and 24 referents without occupational polycyclic aromatic hydrocarbons (PAH) exposure were recruited in this study Urinary 1 hydroxypyrene levels were measured as the internal dose of PAH exposure The 6 per 1 000 of micronucleus value was used as the cut off value to determine whether the individual's chromosomal damage was positive The genotypes of CYP1A1, GSTM1, GSTT1, GSTP1, CYP2E1, NQO1, NAT2 and mEH genes were determined by PCR based methods Multiple logistic regression was used to calculate the adjusted ORs and the 95% CI for the risk of chromosomal damage and to analyze the gene gene interaction Results In 173 subjects, after adjusting the occupational exposure, age, sex, smoking and drinking status, the subjects with GSTM1 null genotype have significantly higher risk for chromosomal damage than subjects with GSTM1 positive genotype (adjusted OR = 2 01, 95% CI =1 03-3 91) Compared with the wild homozygotes at P187S site of NQO1 gene, the variant homozygotes have significantly higher risk for chromosomal damage (adjusted OR =3 18, 95% CI =1 18-8 62) The subjects with variant allele at H113Y site of mEH gene have significantly lower risk for chromosomal damage (adjusted OR =0 40, 95% CI =0 19-0 88) No significant associations were found for other gene polymorphisms and chromosomal damage risk In addition, the gene gene interactions were also found among GSTM1,NQO1 gene P187S and mEH gene H113Y polymorphisms for the risk of chromosomal damage risk Conclusion Significant associations between genetic polymorphisms in GSTM1,NQO1 and mEH gene and risk for chromosomal damage were found among occupational PAH exposed workers, which related to the mechanism of PAH carcinogenesis

关 键 词：焦炉作业工人 外周血淋巴细胞 染色体损伤 遗传易感性 职业暴露 

分 类 号：R131[医药卫生—劳动卫生]