本文選題：苯乙烯 + CYP2E1��； 參考：《沈陽醫(yī)學院》2017年碩士論文

【摘要】：目的本研究通過對苯乙烯作業(yè)工人基因多態(tài)性、淋巴細胞彗星實驗、尿中8-羥基脫氧鳥苷(8-hydroxy-2'-deoxyguanosine,8-OHdG)含量及尿中代謝產(chǎn)物苯乙醇酸(mandelic acid,MA)和苯乙醛酸(phenylglyoxylic acid,PGA)的檢測,探討低濃度苯乙烯對作業(yè)工人尿中代謝產(chǎn)物和DNA損傷的影響,以及CYP2E1和CYP2B6基因多態(tài)性與尿中代謝產(chǎn)物及DNA損傷的相關性,確定苯乙烯敏感遺傳損傷指標及易感性標志物。為保護工人健康及對苯乙烯接觸易感人群篩選提供參考依據(jù)。方法選擇有苯乙烯接觸工齡在1年以上的工人50名為接觸組,同一地區(qū)不接觸苯乙烯及其它已知遺傳毒物的工人48名為對照組。苯乙烯接觸組與對照組相比在性別、年齡、工齡及吸煙比例上具有均衡可比性。通過填寫調(diào)查問卷了解苯乙烯作業(yè)工人一般情況;采用高效液相色譜法(High performance liquid chromatography,HPLC)檢測尿中代謝產(chǎn)物MA和PGA含量;采用酶聯(lián)免疫吸附測定法(enzyme-linked immunosorbent assay,ELISA)檢測尿中8-OHdG含量,單細胞凝膠電泳實驗(single cell gel eletrophoresis,SCGE)檢測DNA鏈斷裂情況;采用聚合酶鏈反應—限制性片段長度多態(tài)性(Polymerase Chain Reaction-Restriction Fragment Length Polymorphism,PCR-RFLP)技術檢測 CYP2E1 及 CYP2B6 基因型的頻率分布情況。結果苯乙烯作業(yè)工人尿中8-OHdG含量及彗星尾長均高于對照組,差異有統(tǒng)計學意義;攜帶CYP2E1野生純合型(C1C1)個體尿中代謝產(chǎn)物MA+PGA含量及尿中8-OHdG含量均高于攜帶突變型(C1C2+C2C2)的個體,差異有統(tǒng)計學意義;攜帶CYP2E1不同基因型個體之間的彗星尾長差異無統(tǒng)計學意義;攜帶CYP2B6基因516GT位點和718AG位點的野生型與突變型個體之間的尿中代謝產(chǎn)物、8-OHdG含量及彗星尾長差異均無統(tǒng)計學意義。結論1.低濃度苯乙烯可導致作業(yè)工人DNA損傷。2.尿中8-OHdG可作為低濃度苯乙烯作業(yè)工人DNA氧化損傷的敏感標志物。3.在低濃度苯乙烯環(huán)境中,CYP2E1突變型基因降低了苯乙烯代謝的能力,攜帶CYP2E1野生型(C1C1)個體為易感性人群。4.CYP2B6兩個突變位點的不同基因型在低濃度苯乙烯環(huán)境中均對苯乙烯代謝無明顯影響。
[Abstract]:Objective to detect the gene polymorphisms of workers exposed to styrene, comet assay of lymphocytes, the content of 8-hydroxy-2guanosine (8-OHdG) in urine and the metabolites of phenylglycolate mandelic acid (MAA) and phenylglyoxylic acid (PGA) in urine. To investigate the effects of low concentration styrene on urinary metabolites and DNA damage in workers, and the relationship between CYP2E1 and CYP2B6 gene polymorphisms, urinary metabolites and DNA damage, and to determine the sensitive genetic damage index and susceptible markers of styrene. To provide a reference for the protection of workers' health and the screening of susceptible population to styrene exposure. Methods 50 workers with exposure to styrene and 48 workers without exposure to styrene and other known genetic poisons in the same area were selected as exposure group. The sex, age, length of service and smoking ratio in the styrene exposure group were balanced and comparable with those in the control group. To find out the general situation of styrene workers by filling out questionnaires; to detect the contents of MA and PGA in urine by high performance liquid chromatographyHPLC, and to detect 8-OHdG in urine by enzyme-linked immunosorbent assay-esa (Elisa), and to measure the content of MA and PGA in urine by high performance liquid chromatography (HPLC) and enzyme-linked immunosorbent assayya Elisa (Elisa). Single cell gel eletrophoresistics (SCGE) was used to detect DNA strand breaks, and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to detect the frequency distribution of CYP2E1 and CYP2B6 genotypes. Results the contents of 8-OHdG and comet tail length in urine of workers exposed to styrene were significantly higher than those of the control group, and the contents of MA PGA and 8-OHdG in urine of individuals carrying CYP2E1 wild homozygous type C1C1) were higher than those of individuals carrying mutant C1C2C2C2). There was no significant difference in comet tail length among individuals with different genotypes of CYP2E1. There was no significant difference in urinary metabolite 8-OHdG content and comet tail length between wild-type and mutant individuals carrying 516GT and 718AG loci of CYP2B6 gene. Conclusion 1. Low concentration of styrene could cause DNA damage. 2. 8-OHdG in urine can be used as a sensitive marker of DNA oxidative damage in workers exposed to low concentration styrene. In low concentration styrene environment, CYP2E1 mutant gene reduced the ability of styrene metabolism. Individuals carrying CYP2E1 wild type C _ 1C _ 1) were susceptible population. 4. Different genotypes of CYP2B6 had no significant effect on styrene metabolism in low concentration styrene environment.
【學位授予單位】：沈陽醫(yī)學院
【學位級別】：碩士
【學位授予年份】：2017
【分類號】：R135

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