氯乙烯作业工人染色体损伤及其遗传易感性

目的 探讨氯乙烯(VCM)致染色体损伤与DNA修复基因和代谢酶基因多态间的关系.方法 收集上海某化工厂402名VCM接触工人健康体检资料、人口学资料(年龄和性别)、生活方式(吸烟、饮酒)和职业接触等因素,评估个人VCM累积接触剂量并分组.采集静脉血3 ml,采用外周血淋巴细胞胞质分裂阻滞微核试验(CBMN)检测染色体损伤,采用聚合酶链式反应(PCR)检测GSTT1、GSTM1基因缺失情况,采用PCR-限制性片段长度多态性技术(RFLP)检测其他基因多态.结果 多元Poisson回归分析结果表明,中(4000～40000 mg)、高(＞40000 mg)VCM接触剂量组染色体损伤的风险明显高于低剂量组,调整后的FR值分别为1.19(1.06～1.34)和1.20(1.06～1.38),差异有统计学意义(P值分别为0.003和0.01);携带CYP2E1和XRCC1 Arg280His突变型基因的个体微核率明显高于野生型个体,调整后的FR值分别为1.12(1.02～1.23)和1.13(1.02～1.25),差异有统计学意义(P值均为0.02);携带GSTP1Val/Val和ALDH2 Glu/Glu基因型个体微核率明显高于其他基因型个体,调整后的FR值分别为0.74(0.59～0.94)和0.87(0.79～0.95),差异有统计学意义(P值分别为0.01和0.003).结论 VCM致染色体损伤与VCM累积接触剂量增高及GSTP1 Val/Val、CYP21E1 c1c2/c2c2、ALDH2 Glu/Glu、XRCC1 280His/His 或Arg/His基因型多态性等因素有关.开展VCM致染色体损伤与遗传易感性方面的研究,有助于VCM致癌机制的阐明,而研究中易感性多态位点的发现也可以为识别易感人群提供理论依据.

Susceptibility of chromosomal damage among workers exposed to vinyl chloride monomer

Objective To explore the association between chromosomal damage induced by vinyl chloride monomer (VCM) and polymorphisms of xenobiotic metabolism genes and DNA repair genes.Methods Cytokinesis-block micronucleus (CBMN) test was performed to detect chromosomal damage in peripheral lymphocytes of 402 VCM-exposed workers.Multiplex PCR was used to simultaneously amplify GSTM1 and GSTT1 genes, other genetic polymorphisms were performed using a PCR-RFLP technique.Results Multiple (adjusted) Poisson regression analysis showed that mean MN frequencies were significantly elevated for the intermediate (4000～40000 mg) and high (＞40000 mg) exposure groups as compared with the low exposure group (P=0.003and 0.03, respectively).For genetic polymorphisms, the exposed workers with CYP2E1 or XRCC1 Arg280His variance showed a higher CBMN frequency than their wild-type homozygous counterparts (P=0.02); so did the workers with GSTP1 105Val/Val genotype or ALDH2 504Glu/Glu genotype than those with a combination of othergenotypes (P=0.01and 0.003, respectively).Conclusion Ourfindings reveal that cumulative exposure doseof VCM and common genetic variants in genes,such as GSTP1,CYP2E1, ALDH2, XRCC1 Arg280His genotypes, are the major factors that modulate MN induction in VCM- exposed workers.Further study to investigate the relationship between individual characteristics and genetic susceptibility to VCM-caused chromosome damage is warranted,it is helpful for us to understand the mechanism of VCM metabolism, to find the biomarkers of susceptibility and to recognize the susceptible individuals in the primary prevention of VCM-caused damage.