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[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 investigate the expression of human 8-oxoguanine DNA glycosylase-1 (hOGG1) and 1X-ray repair cross complementing gene 1 (XRCC1) Relationship between polymorphism of O6-methyl-guanine-DNA methyltransferase (MGMT) and chromosomal damage induced by vinyl chloride in human peripheral blood lymphocytes. [Method] The cytoplasmic block micronucleus test (CBMN) was used to evaluate the chromosomal damage of 313 PVC exposure workers and 141 control workers. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) were used to detect the polymorphism of three sites of XRCC1 gene Arg194Trp, Arg280His and Arg399Gln, Ser326Cys site of hOGG1 gene and Leu84Phe site of MGMT. SAS software packages were used for statistical analysis, and the frequency ratio (FR) and 95% confidence interval (95% CI) were calculated. [Results] The results showed that the micronucleus rate of workers exposed to vinyl chloride was (4.86 ± 2.80) ‰, which was significantly higher than that of the control population (1.22 ± 1.24) ‰ (P <0.01). XRCC1 194Arg / Trp genotype (FR = 1.12, 95% CI: 1.00-1.25; P <0.05) and genotypes of hOGG1 326 Ser / Cys (FR = 1.21, 95% CI: 1.02-1.46; Chromosomal damage occurred in individuals with XRCC1 280 Arg / His and His / His genotypes (FR = 1.12, 95% CI: 1.00-1.26; P <0.05). Among susceptible binaries, individuals carrying CGA / CAG had significantly higher micronuclei rates than those carrying wild-type CGG / CGG (FR = 1.67, 95% CI: 1.19-2.23; P <0.05). The micronucleus rate of the contact group increased significantly with age (FR = 1.13, 95% CI: 1.00-1.28; P <0.05). The combined analysis of XRCC1 genotypes showed that the risk of chromosomal damage was increased as the dose was increased and the number of carrying mutated alleles was increased. [Conclusion] The cytoplasmic blocking micronucleus could be used as a sensitive indicator of early health damage of vinyl chloride exposed workers. The genotypes of XRCC1 Arg194Trp, Arg280His, hOGG1 Ser326Cys, and CGA / CAG with biphasic CGA / CAG and their age may affect the chromosome damage of workers induced by vinyl chloride Have an impact. Cumulative exposure to vinyl chloride and XRCC1 genotype may also have some interaction.