摘要
目的探讨氯乙烯(VCM)暴露工人代谢酶基因多态性与外周血淋巴细胞DNA损伤的关系。方法应用彗星实验测定145名VCM暴露工人外周血淋巴细胞DNA损伤情况,并按DNA损伤情况将工人分为DNA损伤组和对照组,采用病例一对照设计,PCR-RFLP测GSTP1A/G、CYP2E1c1/c2、CYP2D6LG/C基因多态;PCR法测GSTT1、GSTM1缺失情况。同时,通过问卷调查的方式了解被调查者的年龄、性别、吸烟、饮酒和个人职业暴露史。结果GSTP1 AA和AG+GG基因型在DNA损伤组和对照组间的分布频率分别为60.7%,39.3%和78.7%,21.3%,经检验,两组间的分布差异有统计学意义(P〈0.05);GSTT1、GSTM1、CYP2E1和CYP2D6L各基因型的分布频率在DNA损伤组和对照组间的差异无统计学意义(P〉0.05)。多元Logistic回归分析的结果表明,GSTP1多态在氯乙烯所致DNA损伤中的作用与单因素研究结果一致,携带GSTP1 AG+GG基因型的个体较携带GSTPlAA基因型个体DNA损伤的风险性升高(OR=2.48,95%CI:1.11~5.53,P〈0.05);其他因素两组比较,差异无统计学意义(P〉0.05)。结论代谢酶GSTP1基因型与VCM诱导的DNA损伤有关,携带GSTP1 AG或GG基因型个体可能为氯乙烯致DNA损伤的易感人群。
Objective To investigate the association between genetic polymorphisms of metabolizing enzymes and DNA damage in peripheral blood lymphocytes among workers exposed to vinyl chloride monomer (VCM). Methods 145 workers occupationally exposed to VCM were investigated. DNA damage in peripheral blood lymphocytes was measured by Comet assay; the workers were divided into two groups based on the status of DNA damage. Case-control design was used to investigate the relationship between the genetic polymorphisms of metabolizing enzymes and DNA damage. Genotypes of GSTP1A/G, CYP2E1c1/c2 and CYP2D6LG/C were identified by the PCR-RFLP, null genotypes of GSTT1 and GSTM1 were detected by PCR. Individual information including age, gender, smoking, alcohol consumption and occupational exposure history was collected by questionnaire. Results The frequencies of the AA and AG/GG genotype of GSTP1 in DNA damage group and control group were 60.7%, 39.3% and 78. 7%, 21.3% respectively. Significant difference was found in the frequencies of GSTP1 AA and AG/GG genotypes between the two groups(P〈0.05). The frequencies of GSTT1, GSTM1, CYP2E1 and CYP2D6L genotypes in DNA damage group were not significantly different compared with the control group(P〉0.05). The results of multiple logistic regressions were consistent with the single factor χ^2 test, increased risk of DNA damage was significantly associated with GSTP1 AG/GG genotypes (OR = 2.48,95 %CI : 1.11 ~ 5. 53, P〈0. 05) compared with those with GSTP1 AA genotypes, but no significant difference was found in other factors between these two groups. Conclusions The polymorphisms of GSTP1 may be associated with the susceptibility of DNA damage induced by VCM. Subjects carrying GSTP1 AG or GG genotypes could be higher risk of DNA damage when exposed to VCM.
出处
《工业卫生与职业病》
CAS
CSCD
北大核心
2008年第4期193-197,共5页
Industrial Health and Occupational Diseases
基金
国家自然科学基金(30070650
30671740)
复旦大学研究生创新基金资助
关键词
氯乙烯
DNA损伤
代谢酶
基因多态
彗星实验
Vinyl chloride monomer
DNA damage
Metabolizing enzymes
Genetic polymorphism
Comet assay