Department of Occupational Health and Toxicology, School of Public Health, Fudan University, and Key laboratory of public health and safety of Ministry of Education of China, 138 Yixue yuan Road, Shanghai, 200032,China.
Carcinogenesis. 2010 Jun;31(6):1068-73. doi: 10.1093/carcin/bgq075. Epub 2010 Apr 8.
In this study, a group of 313 workers occupationally exposed to vinyl chloride monomer (VCM) and 141 normal unexposed referents were examined for chromosomal damage using the cytokinesis-blocked micronucleus (CBMN) assay in peripheral lymphocytes. We explored the relationship between genetic polymorphisms of XRCC1 (Arg194Trp, Arg280His and Arg399Gln), MGMT(Leu84Phe) and hOGG1 (Ser326Cys) and susceptibility of chromosomal damage induced by VCM. Polymerase chain reaction-restriction fragment length polymorphism techniques were used to detect polymorphisms in XRCC1, hOGG1 and MGMT. It was found that the micronuclei (MN) frequency of exposed workers (4.86 +/- 2.80) per thousand was higher than that of the control group (1.22 +/- 1.24) per thousand (P < 0.01). Increased susceptibility to chromosomal damage as evidenced by higher MN frequency was found in workers with hOGG1 326 Ser/Cys genotype [frequency ratio (FR) = 1.21, 95% confidence interval (CI): 1.02-1.46; P < 0.05], XRCC1 194 Arg/Trp (FR = 1.12, 95% CI: 1.00-1.25; P < 0.05) and XRCC1 280 Arg/His and His/His genotypes (FR = 1.12, 95% CI 1.00-1.26, P < 0.05). Moreover, among susceptibility diplotypes, CGA/CAG carriers had more risk of MN frequency compared with individuals with wild-type CGG/CGG (FR = 1.67, 95% CI: 1.19-2.23; P < 0.05). MN frequency also increased significantly with age in the exposed group (FR = 1.13, 95% CI: 1.00-1.28; P < 0.05). Thus, CB-MN was a sensitive index of early damage among VCM-exposed workers. Genotype XRCC1 Arg194Trp, Arg280His, hOGG1 Ser326Cys, diplotype CGA/CAG and higher age may have an impact on the chromosome damage induced by VCM.
在这项研究中,一组 313 名职业性接触氯乙烯单体(VCM)的工人和 141 名正常未接触的参照者,通过外周血淋巴细胞中的细胞有丝分裂阻断微核(CBMN)试验,检查了染色体损伤情况。我们探讨了 XRCC1(Arg194Trp、Arg280His 和 Arg399Gln)、MGMT(Leu84Phe)和 hOGG1(Ser326Cys)基因多态性与 VCM 诱导的染色体损伤易感性之间的关系。聚合酶链反应-限制性片段长度多态性技术用于检测 XRCC1、hOGG1 和 MGMT 的多态性。结果发现,暴露组工人的微核(MN)频率(4.86 ± 2.80)/千高于对照组(1.22 ± 1.24)/千(P < 0.01)。结果发现,hOGG1 326 Ser/Cys 基因型的工人(MN 频率比值(FR)=1.21,95%置信区间(CI):1.02-1.46;P < 0.05)和 XRCC1 194 Arg/Trp(FR = 1.12,95%CI:1.00-1.25;P < 0.05)和 XRCC1 280 Arg/His 和 His/His 基因型的工人的染色体损伤易感性增加,易感性二倍体,与野生型 CGG/CGG 个体相比,CGA/CAG 携带者的 MN 频率更高(FR = 1.67,95%CI:1.19-2.23;P < 0.05)。此外,在暴露组中,MN 频率随着年龄的增长而显著增加(FR = 1.13,95%CI:1.00-1.28;P < 0.05)。因此,CB-MN 是 VCM 暴露工人早期损伤的敏感指标。XRCC1 Arg194Trp、Arg280His、hOGG1 Ser326Cys 基因型、CGA/CAG 二倍体和较高年龄可能对 VCM 引起的染色体损伤有影响。