本文選題：苯乙烯 + CYP2E1��； 參考：《沈陽(yáng)醫(yī)學(xué)院》2017年碩士論文

【摘要】：目的本研究通過(guò)對(duì)苯乙烯作業(yè)工人基因多態(tài)性、淋巴細(xì)胞彗星實(shí)驗(yàn)、尿中8-羥基脫氧鳥(niǎo)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(cè),探討低濃度苯乙烯對(duì)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(guān)性,確定苯乙烯敏感遺傳損傷指標(biāo)及易感性標(biāo)志物。為保護(hù)工人健康及對(duì)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(duì)照組。苯乙烯接觸組與對(duì)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(guò)填寫(xiě)調(diào)查問(wèn)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(cè)尿中代謝產(chǎn)物MA和PGA含量;采用酶聯(lián)免疫吸附測(cè)定法(enzyme-linked immunosorbent assay,ELISA)檢測(cè)尿中8-OHdG含量,單細(xì)胞凝膠電泳實(shí)驗(yàn)(single cell gel eletrophoresis,SCGE)檢測(cè)DNA鏈斷裂情況;采用聚合酶鏈反應(yīng)—限制性片段長(zhǎng)度多態(tài)性(Polymerase Chain Reaction-Restriction Fragment Length Polymorphism,PCR-RFLP)技術(shù)檢測(cè) CYP2E1 及 CYP2B6 基因型的頻率分布情況。結(jié)果苯乙烯作業(yè)工人尿中8-OHdG含量及彗星尾長(zhǎng)均高于對(duì)照組,差異有統(tǒng)計(jì)學(xué)意義;攜帶CYP2E1野生純合型(C1C1)個(gè)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(gè)體,差異有統(tǒng)計(jì)學(xué)意義;攜帶CYP2E1不同基因型個(gè)體之間的彗星尾長(zhǎng)差異無(wú)統(tǒng)計(jì)學(xué)意義;攜帶CYP2B6基因516GT位點(diǎn)和718AG位點(diǎn)的野生型與突變型個(gè)體之間的尿中代謝產(chǎn)物、8-OHdG含量及彗星尾長(zhǎng)差異均無(wú)統(tǒng)計(jì)學(xué)意義。結(jié)論1.低濃度苯乙烯可導(dǎo)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(biāo)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(gè)體為易感性人群。4.CYP2B6兩個(gè)突變位點(diǎn)的不同基因型在低濃度苯乙烯環(huán)境中均對(duì)苯乙烯代謝無(wú)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(xué)位授予單位】：沈陽(yáng)醫(yī)學(xué)院
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類(lèi)號(hào)】：R135

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