Abstract:
Objective To explore the relationship between genetic polymorphism of x-ray repair cross complementing gene 1 (XRCC1), human 8-oxoguanine DNA glycosylase-1 (hOGG1) and O6-methylguanine DNA methyltransferase (MGMT)) and susceptibility of chromosomal damage induced by vinyl chloride monomer (VCM).
Methods A total of 313 workers occupationally exposed to VCM and 141 normal individuals were involved. Cytokinesis-block micronucleus (CBMN) assay was used to detect chromosome damage in peripheral lymphocyte. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique was applied to detect polymorphisms in XRCC1 (Arg194Trp, Arg280His, Arg399Gln), MGMT (Leu84Phe) and hOGG1 (Ser326Cys) of the exposed workers. Statistical analysis was performed using SAS software to calculate frequency ratio (FR) and 95% confidence interval (95%CI).
Results The micronucleus (MN) frequency of the exposed workers(4.86& #177;2.80) ‰ was significantly higher than that of the controls(1.22& #177;1.24)‰(P<0.01). Workers who carried the hOGG1 326 Ser/Cys genotype (FR=1.21, 95%CI:1.02-1.46; P<0.05), the XRCC1 194 Arg/Trp genotype (FR=1.12, 95%CI:1.00-1.25; P<0.05), and the XRCC1 280 Arg/His and His/His genotypes (FR=1.12, 95%CI:1.00-1.26; P<0.05) were more susceptible to chromosome damage. Moreover, among susceptibility diplotypes, CGA/CAG carriers had more risks of MN frequency compared with individuals with wild-type CGG/CGG (FR=1.67, 95%CI:1.19-2.23; P<0.05). Among the exposed workers, the MN frequency also increased significantly with age (FR=1.13, 95%CI:1.00-1.28; P<0.05). In addition, the higher exposure level was and the more number of allele genes in XRCC1 were, the more serious chromosome damage in VCM exposed workers would be.
Conclusion CBMN may be used as a sensitive index to early damage in VCM exposed workers. Genotype XRCC1 Arg194Trp, Arg280His, hOGG1 Ser326Cys, diplotype CGA/CAG and age may have effects on the chromosome damage induced by VCM. Exposure level and genotype of XRCC1 may have interaction effects.
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