Research Of Relationship About DNA Repair Genetic Polymorphisms And Susceptibility Of Genetic Damage Among Benzene-exposed Workers

Objective: Benzene is an important raw materials in industrial production, and theproduction and consumption of benzene in recent years has been in the growth, theannual growth rate is over10%. Benzene has a major potential hazard to human health.Occupational epidemiological survey found that the benzene poisoning was associatedwith individual susceptibility, it was the result of the role of environmental factors andgenetic factors. This study aimed to explor whether occupational benzene exposure underthe current standards would cause heath hazards and genetic damage, and to detectsusceptibility biomarker of benzene-exposed workers. Methods: The subjects of thisstudy came from one automobile manufacturing factory of Anhui province in China. Thehealth status of benzene-exposed workers was obtained through health examination andgenetic damage detecting. The relationship between benzene exposure and chromosomedamage was explored in this study. Cytokinesis-block micronucleus (CB-MN) assay wasused to detect chromosome damage in peripheral lymphocyte. PCR-RFLP andCRS-RFLP technique was applied to detect genes polymorphisms. Through exploring theassociation between several key gene polymorphisms in DNA repair pathways and therisk of benzene-induced genetic damage, we identified the susceptible biomarkers,including XRCC1gene, APE1gene, the XPC gene, hOGG1gene, MGMT gene, andhMYH genes. SPSS16.0software was applicated in this study. Results:1) The benzeneconcentration of the workplace air monitoring sites＜0.6mg/m3was lower than thenational occupational exposure limit; the utilization rate of protective equipment wasonly63.0%in benzene-exposed workers, and benzene-exposed workers had less aware ofself-protection.2) There was not associated between the clinical symptoms of workersand the benzene exposure, such as insomnia and more dreams, dizziness, headache,bleeding gums, nasal bleeding, ecchymosis, abnormal menstruation, et al (P＞0.05); lowlevel benzene exposure could lead to the rate increases of white blood cells abnormality (fluctuation or reduction) and red blood cells reduction (P＜0.001). Logistic regressionanalysis showed that the main factors of white blood cell abnormality (fluctuation orreduction) were benzene exposure, length of service and age, the main factor of red bloodcell reduction was benzene exposure. Hemoglobin and platelet count were no significantdifferences in different groups (P＞0.05).3) The MN frequency of the exposed group(2.12‰±1.87‰) was significantly higher than that of the control group(1.19‰±1.68‰)(P＜0.001), Multi-factor Poisson regression analysis found thatwomen, older age (＞35years) and benzene exposure were the risk factors of increasingmicronucleus rate. The95-percentile of the controls CBMN (i.e.4‰) distribution, maybeused to define chromosomal damage caused by benzene-exposure, above which the MNfrequency may indicate an aberration from being normal, hence indicating chromosomaldamage; the MN frequency of the exposed groups according to the classification of WBCwas significantly higher than that of the control group (P＜0.001), and the MN frequencyof benzene-exposed with WBC normal group was significantly higher than that of thecontrol group by54%, FR (95%CI) was1.54(1.23～1.95).4) In control group, this studyshowed that the MN frequency of the subjects with XRCC1399AA genotype wassignificantly higher than those with XRCC1399GG genotype (P＜0.05), FR (95%CI)was2.44(1.30～4.33); the MN frequency of the subjects with XPC.PAT PAT+/+genotype was significantly higher than those with XPC.PAT PAT-/-genotype (P＜0.05),FR (95%CI) was2.40(1.44～3.92); the MN frequency of the subjects with XPC499TTor XPC499(CT+TT) genotype was significantly lower than those with XPC499CCgenotype (P＜0.05), FR (95%CI) was0.28(0.08～0.68) or0.62(0.42～0.92); the MNfrequency of the subjects with XPC939AC or XPC939(AC+CC) genotype wassignificantly lower than those with XPC939AA genotype (P＜0.05), FR (95%CI) was0.51(0.33～1.30) or0.54(0.37～0.79); the MN frequency of the subjects withhOGG1326GG genotype was significantly higher than those with hOGG1326CCgenotype (P＜0.05), FR (95%CI) was1.97(1.10～3.84); others genetic polymorphismswere not significantly different compared with wild-type (P＞0.05).5) Inbenzene-exposed workers, this study showed that the MN frequency of the subjects withXRCC1280AA genotype was significantly lower than those with XRCC1280GGgenotype (P＜0.05), FR (95%CI) was0.40(0.14～0.86); the MN frequency of thesubjects with MGMT84(CT+TT) genotype was significantly lower than those withMGMT84CC genotype (P＜0.05), FR (95%CI) was0.85(0.72～0.99); others geneticpolymorphisms were not significantly different compared with wild-type (P＞0.05).6) Multivariate Poisson regression analysis suggested that the impact factors ofmicronucleus include age, gender, drinking, XPC939and APE1148in control group,older age (＞35years) and female were risk factors, and drinking, XPC939mutant geneand APE1148mutant gene were protective factors. While age, XPC.PAT, and MGMT84were impact factors in exposure group, older age (＞35years) was risk factors, andXPC.PAT (PAT+) gene and MGMT84mutant gene were protective factors.7) Diplotypeanalysis of relationship between MN frequency and diplotype of194,280,399sites ofXRCC1gene demonstrated that the MN frequency in subjects with AAA/BAA,AAB/AAB,ABA/ABA,ABB/ABB (A: wild allele; B: variant allele) was significantlyhigher than that in subjects with AAA/AAA in benzene-exposed group (P＜0.05).Diplotype analysis of relationship between MN frequency and diplotype of499, PAT,939sites of XPC gene demonstrated that the MN frequency in subjects with ABB/ABB wassignificantly higher than that in subjects with AAA/AAA in benzene-exposed group (P＜0.05). Conclusion: Occupational benzene exposure could induce chromosome damageeven when the exposure level was lower than the national occupational health standard ofChina. Chromosome damage based on CBMN could be a reference index to assessmentlow level occupational benzene exposure. MN frequency had certain application value asa effect biomarker in low level benzene exposure. Some of the polymorphisms of DNArepair genes and diplotypes may be associated with chromosome damage inbenzene-exposed workers.