OBJECTIVETo explore the relationship between genetic polymorphism of P53, P21, CCND1 and susceptibility of chromosomal damage induced by vinyl chloride monomer (VCM).

METHODS183 workers occupationally exposed to VCM were involved in our study. Cytokinesis-block micronucleus (CB-MN) assay was used to detect chromosome damage in peripheral lymphocyte. PCR-RFLP technique was applied to detect polymorphisms in P53 gene (exon4, intron3 and intron6), P21 gene (exon2 and exon3) and CCND1 (exon4).

RESULTSThe risk of chromosomal damage for VCM-exposed workers with more than 30 yr was 1.2202 (95% CI: 1.0580 approximately 1.4072, P = 0.0062) compared with the younger workers, and the risk of female workers was 1.1491 (95% CI: 0.9841 approximately 1.3416, P = 0.0772) compared with male workers. The MN frequency in subjects with P53 intron6 mutant homozygous and heterozygous was higher than their wild-type homozygous counterparts (OR = 1.3032, 95% CI: 1.1285 approximately 1.6405, P = 0.0285). P53 exon4, intron3 and intron6 haplotype pairs of BBB/AAA and BAB/AAA were associated with the increased frequencies of micronucleus.

CONCLUSIONAmong VCM-exposed workers, more than 30ys, female, carrying P53 intron6 mutated allele and BBB/AAA and BAB/AAA haplotype pairs have higher risk of chromosomal damage.

Cell Cycle Checkpoints ; Humans ; Micronucleus Tests ; Occupational Exposure ; Polymorphism, Genetic ; Vinyl Chloride

OBJECTIVETo explore the association between chromosomal damage induced by vinyl chloride monomer (VCM) and polymorphisms of xenobiotic metabolism genes and DNA repair genes.

METHODSCytokinesis-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.

RESULTSMultiple (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).

CONCLUSIONOur 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.

Adult ; Chromosome Aberrations ; DNA Damage ; DNA Repair ; Female ; Genetic Predisposition to Disease ; Genotype ; Humans ; Male ; Micronucleus Tests ; Middle Aged ; Occupational Exposure ; Vinyl Chloride ; toxicity ; Young Adult