Ji Fang, Zheng Ying-Jia, Wang Qi, Wang Wei, Qiu Yu-Lan, Wu Fen, Chai Shang-Jian, Li Jun, Xia Zhao-Lin
Department of Occupational Health, School of Public Health, Fudan University, Key Laboratory of Public Health Safety, Ministry of Education, Shanghai, China.
Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi. 2011 Aug;29(8):583-8.
To explore the association between chromosomal damage induced by vinyl chloride monomer (VCM) and polymorphisms of xenobiotic metabolism genes and DNA repair genes.
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.
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 = 0.003 and 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 other genotypes (P = 0.01 and 0.003, respectively).
Our findings reveal that cumulative exposure dose of 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.
探讨氯乙烯单体(VCM)诱导的染色体损伤与外源性物质代谢基因及DNA修复基因多态性之间的关联。
采用胞质分裂阻滞微核(CBMN)试验检测402名VCM暴露工人外周血淋巴细胞中的染色体损伤。运用多重PCR同时扩增GSTM1和GSTT1基因,其他基因多态性采用PCR-RFLP技术进行检测。
多重(校正)泊松回归分析显示,与低暴露组相比,中暴露组(4000 - 40000 mg)和高暴露组(> 40000 mg)的平均微核频率显著升高(P值分别为0.003和0.03)。对于基因多态性,携带CYP2E1或XRCC1 Arg280His变异的暴露工人的CBMN频率高于其野生型纯合子对应者(P = 0.02);携带GSTP1 105Val/Val基因型或ALDH2 504Glu/Glu基因型的工人的CBMN频率也高于其他基因型组合的工人(P值分别为0.01和0.003)。
我们的研究结果表明,VCM的累积暴露剂量以及GSTP1、CYP2E1、ALDH2、XRCC1 Arg280His基因型等基因中的常见遗传变异是调节VCM暴露工人微核诱导的主要因素。有必要进一步研究个体特征与VCM所致染色体损伤遗传易感性之间的关系,这有助于我们理解VCM代谢机制,寻找易感性生物标志物,并在VCM所致损伤的一级预防中识别易感个体。