Genetic susceptibility of DNA damage induced by vinyl chloride monomer exposure.
- Author:
Fang JI
1
;
Shou-Min ZHU
;
Ai-Hong WANG
;
Ya-Bin QU
;
Shou-Yong GU
;
Ren ZHU
;
Shang-Jian CAI
;
Jun LI
;
Zhao-Lin XIA
Author Information
- Publication Type:Journal Article
- MeSH: Case-Control Studies; Comet Assay; DNA Damage; drug effects; Female; Genetic Predisposition to Disease; Genotype; Humans; Male; Occupational Exposure; Polymorphism, Single Nucleotide; Vinyl Chloride; toxicity; Workplace
- From: Chinese Journal of Industrial Hygiene and Occupational Diseases 2010;28(1):12-17
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo explore the association between DNA damage induced by vinyl chloride monomer (VCM) and polymorphisms of DNA repair genes and xenobiotic metabolism genes of VCM.
METHODSComet assay was employed to detect DNA damage. Based on the status of DNA damage, the VCM exposure workers were divided into two groups: DNA damage group (75) and control group (75). Case-control design was used to investigate the association between the genetic polymorphisms and DNA damage induced by VCM. Genotypes of XRCC1 (Arg194Trp, Arg280His and Arg399Gln), XPD (Ile199Met, Asp312Asn and Lys751Gln) and CYP2E1 were identified by the PCR-RFLP. PCR assay was used to detect positive and null genotype of GSTT1 and GSTM1.
RESULTSUnivariate analysis showed that the CYP2E1 c1c2/c2c2 and XPD751 Lys/Gln and Gln/Gln genotypes were significantly associated with the increased levels of DNA damage, XRCCI 339 Arg/Gln and Gln/Gln genotypes were significantly associated with the decreased levels of DNA damage (P < 0.01, P < 0.05, respectively). Logistic regression analysis showed that there was significant association between the genotypes of XRCC1 194, XRCC1 399, XPD 751, CYP2E1 and DNA damages. A prominent risk decreasing of DNA damage was observed for those individuals possessing XRCC1 399Arg/Gln + Gln/Gln genotypes (OR: 0.35, 95%CI: 0.12 approximately 1.01, respectively); The results also showed that there were significant associations between CYP2E1 c1c2/c2c2 and DNA damage both in high and low VCM-exposed groups (OR: 2.57, 95%CI: 1.01 approximately 6.59 and OR: 2.57, 95%CI: 0.99 approximately 6.87).
CONCLUSIONCumulative exposure dose and genotypes of XRCC1 194, XRCC1 399, XPD 751 and CYP2E1 may modulate the DNA damage induced by VCM exposure.