摘要
[目的]探讨DNA损伤修复基因X线修复交叉互补基因（1X-ray repair cross complementing gene 1,XRCC1）、人8-羟基鸟苷糖苷酶1基因（human 8-oxoguanine DNA glycosylase-1,hOGG1）以及O6-甲基鸟嘌呤-DNA甲基转移酶基因（O6-methyl-guanine DNA methyltransferase,MGMT）的多态性与氯乙烯致人外周血淋巴细胞染色体损伤的关系。[方法]采用胞质阻滞微核试验方法（CBMN）评价313名氯乙烯接触工人和141名对照工人染色体损伤水平,应用聚合酶链反应-限制性片段多态性技术（polymerase chain reaction-restriction fragment length polymorphism,PCR-RFLP）对接触工人XRCC1基因Arg194Trp、Arg280His和Arg399Gln 3个位点和hOGG1基因Ser326Cys位点及MGMT基因Leu84Phe位点进行多态性检测。采用SAS软件包进行统计分析,计算率比（frequency ratio,FR）及其95%可信限（95%confidence interval,95%CI）。[结果]本研究表明,氯乙烯接触工人的微核率为（4.86±2.80）‰,显著高于对照人群的微核率（1.22±1.24）‰（P〈0.01）。携带hOGG1 326 Ser/Cys基因型（FR=1.21,95%CI：1.02~1.46;P〈0.05）、XRCC1 194Arg/Trp基因型（FR=1.12,95%CI：1.00~1.25;P〈0.05）和XRCC1 280 Arg/His和His/His基因型（FR=1.12,95%CI：1.00~1.26;P〈0.05）的个体均易发生染色体损伤。在易感性的双体型中,携带CGA/CAG的个体相比携带野生型CGG/CGG的个体微核率明显升高（FR=1.67,95%CI：1.19~2.23;P〈0.05）。接触组人群的微核率随着年龄的增长显著升高（FR=1.13,95%CI：1.00~1.28;P〈0.05）。对XRCC1基因型进行联合分析,发现随着剂量增加和携带突变等位基因数目增多,其染色体损伤风险增大。[结论]胞质阻滞微核可以作为氯乙烯接触工人早期健康损害的敏感指标,基因型XRCC1 Arg194Trp、Arg280His、hOGG1 Ser326Cys和双体型CGA/CAG以及年龄增长可能对氯乙烯致工人染色体损伤的过程产生影响。氯乙烯累积接触水平与XRCC1基因型也可能存在一定的交互作用�
[Objective] To explore the relationship between genetic polymorphism of x-ray repair cross complementing gene 1（XRCC1）,human 8-oxoguanine DNA glycosylase-1（hOGG1） and O6-methylguanine DNA methyltransferase（MGMT） and susceptibility of chromosomal damage induced by vinyl chloride monomer（VCM）.[Methods] A total of 313 workers occupationally exposed to VCM and 141 normal individuals were involved.Cytokinesis-block micronucleus（CBMN） assay was used to detect chromosome damage in peripheral lymphocyte.Polymerase chain reaction-restriction fragment length polymorphism（PCR-RFLP） technique was applied to detect polymorphisms in XRCC1（Arg194Trp,Arg280His,Arg399Gln）,MGMT（Leu84Phe） and hOGG1（Ser326Cys） of the exposed workers.Statistical analysis was performed using SAS software to calculate frequency ratio（FR） and 95% confidence interval（95%CI）.[Results] The micronucleus（MN） frequency of the exposed workers [（4.86±2.80）‰] was significantly higher than that of the controls [（1.22±1.24）‰]（P 0.01）.Workers who carried the hOGG1 326 Ser/Cys genotype（FR=1.21,95%CI： 1.02-1.46;P 0.05）,the XRCC1 194 Arg/Trp genotype（FR=1.12,95%CI： 1.00-1.25;P 0.05）,and the XRCC1 280 Arg/His and His/His genotypes（FR=1.12,95% CI： 1.00-1.26;P 0.05） were more susceptible to chromosome damage.Moreover,among susceptibility diplotypes,CGA/CAG carriers had more risks of MN frequency compared with individuals with wild-type CGG/CGG（FR=1.67,95%CI： 1.19-2.23;P 0.05）.Among the exposed workers,the MN frequency also increased significantly with age（FR=1.13,95%CI： 1.00-1.28;P 0.05）.In addition,the higher exposure level was and the more number of allele genes in XRCC1 were,the more serious chromosome damage in VCM exposed workers would be.[Conclusion] CBMN may be used as a sensitive index to early damage in VCM exposed workers.Genotype XRCC1 Arg194Trp,Arg280His,hOGG1 Ser326Cys,diplotype CGA/CAG and age may have effects on the chromosome damage induced by VCM.Exposure leve
出处
《环境与职业医学》
CAS
北大核心
2012年第4期197-202,共6页
Journal of Environmental and Occupational Medicine
基金
国家自然科学基金(编号:30671740)
上海市公共卫生重点学科建设计划(编号:08GW2X0402)
