OBJECTIVE: To evaluate whether base excision repair gene polymorphisms contributed to susceptibility of chromosomal damage induced by vinyl chloride monomer (VCM). METHODS: Cytokinesis block micronucleus test was performed on 185 VCM-exposed workers to detect chromosomal damage in peripheral lymphocytes. The PCR-restriction fragment length polymorphism technique was applied to detect polymorphisms of TDG, PARP1, and APE1 genes. Univariate and multivariate Poisson regression analysis was performed. RESULTS: There was a 1.198-fold increased micronucleus frequency for individuals carrying TDG 199Gly/Ser + Ser/Ser genotypes compared with those carrying Gly/Gly genotype (P < 0.05). Individuals with the combined genotypes of TDG 199Gly/Ser + Ser/Ser and APE1 64Ile/Val + Val/Val had a significantly increased micronucleus frequency compared with those carrying wild-type genotypes for both genes. CONCLUSION: VCM-exposed workers carrying TDG 199Gly/Ser + Ser/Ser genotypes were susceptible to chromosomal damage. A combination of TDG Gly199Ser and APE1 Ile64Val polymorphisms may modify the risk of chromosomal damage.
OBJECTIVE: To evaluate whether base excision repair gene polymorphisms contributed to susceptibility of chromosomal damage induced by vinyl chloride monomer (VCM). METHODS: Cytokinesis block micronucleus test was performed on 185 VCM-exposed workers to detect chromosomal damage in peripheral lymphocytes. The PCR-restriction fragment length polymorphism technique was applied to detect polymorphisms of TDG, PARP1, and APE1 genes. Univariate and multivariate Poisson regression analysis was performed. RESULTS: There was a 1.198-fold increased micronucleus frequency for individuals carrying TDG 199Gly/Ser + Ser/Ser genotypes compared with those carrying Gly/Gly genotype (P < 0.05). Individuals with the combined genotypes of TDG 199Gly/Ser + Ser/Ser and APE1 64Ile/Val + Val/Val had a significantly increased micronucleus frequency compared with those carrying wild-type genotypes for both genes. CONCLUSION: VCM-exposed workers carrying TDG 199Gly/Ser + Ser/Ser genotypes were susceptible to chromosomal damage. A combination of TDG Gly199Ser and APE1Ile64Val polymorphisms may modify the risk of chromosomal damage.
Authors: Ingo Ruczinski; Timothy J Jorgensen; Yin Yao Shugart; Yvette Berthier Schaad; Bailey Kessing; Judith Hoffman-Bolton; Kathy J Helzlsouer; W H Linda Kao; Lee Wheless; Lesley Francis; Rhoda M Alani; Paul T Strickland; Michael W Smith; Anthony J Alberg Journal: Carcinogenesis Date: 2012-05-11 Impact factor: 4.944