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 = 0.003 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).
Conclusion: 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.