Effects Of CYP2E1 And CYP2B6 Genetic Polymorphisms On Urinary Metabolites And DNA Damage Of Workers Exposed To Styrene

ObjectiveThrough the genetic polymorphism of the workers exposed to styrene,the comet assay of the lymphocytes,the content of 8-hydroxy-2'-deoxyguanosine(8-OHdG)and the metabolites of mandelic acid(MA)and phenylglyoxylic acid(PGA)in the urine were determined,to investigate the effects of low concentration of styrene on the urinary metabolites and DNA damage and the correlation between CYP2E1 and CYP2B6 genetic polymorphisms and urinary metabolites and DNA damage.To determine the sensitive genetic damage index and genetic susceptibility markers of styrene,to provide reference for protecting workers' health and screening for susceptibility to styrene exposure.MethodsA group of 50 workers who had been exposed to styrene for more than 1 years were selected as the exposure group,and the other workers in the same area who were not exposed to styrene and other known genetic toxicants were selected as the control group.Styrene exposure group compared with the control group in gender,age,length of service and smoking habits,with a balanced comparability.To understand the general situation of workers exposed to styrene through the questionnaire;High performance liquid chromatography(HPLC)was used to detect the contents of metabolites of MA and PGA in urine;Enzyme linked immunosorbent assay(ELISA)was used to detect the content of 8-OHdG in urine,single cell gel electrophoresis(SCGE)was used to detect DNA strand breaks and the frequency distribution of CYP2E1 and CYPC2B6 genotype was detected by polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP).ResultsThe comet tail length and the content of 8-OHdG in the urine of workers exposed to styrene were higher than those in the control group,the difference was statistically significant;8-OHdG content and the metabolites of MA+PGA content in urine of the individuals carrying CYP2E1 homozygous wild type(C1C1)were higher than those of individuals carrying the mutant(C1C2+C2C2),the difference was statistically significant;there were no statistically significant differences in the contents of MA +PGA,8-OHdG and comet tail length between the wild type and mutant individuals carrying the CYP2B6 gene the 516G>T and the 718A>G site.Conclusions1.Low concentrations of styrene could lead to DNA damage in workers.2.Urinary 8-OHdG could be an sensitive marker of DNA oxidative damage in workers exposed to low concentrations of styrene.3.In the low concentration of styrene environment,CYP2E1 mutant genes reduce the ability of styrene metabolism,carrying CYP2E1 wild type(C1C1)individuals as the susceptible population.4.Different genotypes of CYP2B6 at two mutation sites had no significant effects on styrene metabolism in low concentration styrene environment.