本文關(guān)鍵詞：苯乙烯致DNA損傷及相關(guān)調(diào)控酶mRNA表達橫斷面研究　出處：《濟南大學(xué)》2012年碩士論文　論文類型：學(xué)位論文

  更多相關(guān)文章： 苯乙烯 職業(yè)健康危害 DNA損傷 雙核微核 mRNA表達

【摘要】：【研究目的】 1.了解職業(yè)苯乙烯工人接觸水平及健康損害情況； 2.探討苯乙烯對職業(yè)工人的遺傳損傷效應(yīng)； 3.以實時熒光定量為檢測平臺，探討接觸不同苯乙烯暴露水平對甲基轉(zhuǎn)移酶、乙�；竚RNA表達的影響。尋找其職業(yè)危害的生物標志物，為職業(yè)接觸人群的健康監(jiān)護及危險度評價提供理論依據(jù)，達到加強病因預(yù)防的目的。 【研究方法】 1.采用定點及個體采樣獲取不同暴露工人苯乙烯接觸水平并通過苯乙烯作業(yè)工人職業(yè)衛(wèi)生學(xué)調(diào)查及相應(yīng)的職業(yè)健康體檢，獲取工人健康狀況基礎(chǔ)數(shù)據(jù)； 2.采用胞質(zhì)分裂阻滯微核實驗對不同暴露苯乙烯水平的作業(yè)工人進行細胞遺傳毒性效應(yīng)研究； 3.以SYBR Green I嵌合實時熒光定量聚合酶鏈式反應(yīng)法檢測相關(guān)DNA甲基轉(zhuǎn)移酶DNMT1、DNMT3a、DNMT3b、組蛋白甲基化酶HMT和甲基CPG結(jié)合蛋白(MeCP2)以及蛋白乙酰轉(zhuǎn)移酶HAT、組蛋白去乙酰酶HDAC的mRNA含量表達，探討不同苯乙烯暴露工人對5種相關(guān)甲基轉(zhuǎn)移酶和2種相關(guān)乙�；竚RNA表達，初步探討表觀遺傳對相關(guān)調(diào)控酶的調(diào)控作用,尋找合適的生物標志物。 【研究結(jié)果】 1.苯乙烯作業(yè)工人健康損害 定點及個體檢測顯示苯乙烯接觸工人均處于苯乙烯高暴露水平；暴露組工人咳嗽、頭暈等癥狀的發(fā)生率明顯高于對照組工人（P＜0.05），接觸丙酮、稀料等其他有機溶劑是危險因素，其OR=8.920,95%CI(3.405,23.368）。兩組臨床體檢結(jié)果如肝功、血常規(guī)、心電圖、尿常規(guī)、肝膽腎B超檢查等差異均無顯著性（P＞0.05）。 2.苯乙烯對DNA損傷檢測 苯乙烯暴露組淋巴細胞微核率高于對照組，其DNA損傷程度差異有顯著性(P＜0.05)，兩組在性別間無差異（P＞0.05），未觀察到吸煙、飲酒等因素對微核率有影響（P＞0.05）。 3.苯乙烯對甲基轉(zhuǎn)移酶、乙�；竚RNA表達的影響 苯乙烯暴露組DNA甲基轉(zhuǎn)移酶DNMT1及組蛋白乙�；窰AT1mRNA高表達于對照組，差異顯著（其P值分別為0.005,＜0.001），組蛋白甲基化酶HMT mRNA表達在兩組間差異也具有統(tǒng)計學(xué)意義（P＜0.05）；DNA甲基轉(zhuǎn)移酶DNMT3A、DNMT3B、甲基CPG結(jié)合蛋白MeCP2以及組蛋白去乙酰酶HDAC mRNA表達含量兩組比較差異無統(tǒng)計學(xué)意義（P＞0.05）。在男性組中僅有HAT1的mRNA相對表達含量暴露組高于對照組，差異具有統(tǒng)計學(xué)意義（P＜0.001）；在女性組中DNMT1mRNA及HAT1mRNA的相對表達含量，暴露組明顯高于對照組，具有顯著性差異（P值分別為0.002，0.001），其他調(diào)控酶mRNA的表達差異不顯著（P＞0.05）。 【研究結(jié)論】 1.苯乙烯能夠引起工人如咳嗽、頭暈等癥狀的發(fā)生，并且在丙酮、稀料等有機溶劑的作用下會加劇機體反應(yīng)程度。短年限暴露苯乙烯對工人的身體損傷不明顯，其損傷效應(yīng)還有待于繼續(xù)觀察。 2.苯乙烯暴露對人外周血淋巴細胞微核率有影響，并呈現(xiàn)一定的遺傳毒性作用，雙核微核可作為其早期遺傳損傷的指標。 3.苯乙烯暴露可引起基因表達調(diào)控酶DNMT1、HMT及HAT1的mRNA不同程度的高表達，可作為其遺傳損傷早期效應(yīng)標志物，而對其他基因表達調(diào)控酶DNMT3a、DNMT3b、MeCP2及HDAC10的mRNA表達沒有顯著影響。HAT1mRNA在苯乙烯暴露的男性組、女性組中均高表達，DNMT1mRNA在女性苯乙烯暴露組中高表達，，其他調(diào)控酶如DNMT3a,DNMT3b, HMT, MeCP2及HDAC10的mRNA表達在不同性別暴露組沒有顯著影響。
[Abstract]:[purpose]
1. understand the occupational exposure level and health damage of occupational styrene workers.
2. to investigate the genetic damage effect of styrene on occupational workers.
3. by real-time fluorescent quantitative detection platform, to contact different styrene exposure level of methyl transferase, effect of acetyltransferase mRNA expression. The occupation harm biomarkers provide a theoretical basis for health monitoring and risk assessment for the occupation with people, to strengthen the etiology and prevention.
[research method]
1., the level of styrene exposure of different exposed workers was obtained by fixed point sampling and individual sampling, and the basic data of workers' health status were obtained through occupational hygienic investigation and occupational health examination of styrene workers.
The 2. study of the genotoxicity of cytokinesis block micronucleus test on different levels of workers exposed to styrene;
3. to detect DNA methyl SYBR Green I embedded real-time fluorescence quantitative polymerase chain reaction method transferase DNMT1, DNMT3a, DNMT3b, histone methyltransferase HMT and methyl CPG binding protein (MeCP2) and histone acetyltransferase HAT, histone deacetylase HDAC mRNA content of styrene exposed workers to investigate. 5 related methyltransferases and 2 related acetyltransferase mRNA expression, to explore the epigenetic regulation of genetic regulatory enzymes, to find suitable biomarkers.
[results]
Health damage of 1. styrene workers
Fixed point and individual test showed that styrene exposed workers styreneat high exposure level of workers exposed group; cough, dizziness and other symptoms were significantly higher than control group workers (P < 0.05), contact acetone and other organic solvents thinners and other risk factors, the OR=8.920,95% CI (3.405,23.368). Two groups of clinical examination results such as liver function. Blood routine, urine routine, ECG, liver and kidney were not significantly difference B ultrasound examination (P > 0.05).
Detection of DNA damage by 2. styrene
In the styrene exposure group, the lymphocyte micronucleus rate was higher than that in the control group, and the difference of DNA damage was significant (P < 0.05). There was no difference between the two groups in gender (P > 0.05). No smoking or drinking was observed on the micronucleus rate (P > 0.05).
Effect of 3. styrene on the expression of methyltransferase and acetyltransferase mRNA
Styrene exposure group DNA methyltransferase DNMT1 and histone deacetylase HAT1mRNA high expression in the control group, significant difference (P = 0.005, P < 0.001), histone methyltransferase HMT mRNA expression in the difference between the two groups was statistically significant (P < 0.05); DNA methyltransferase DNMT3A. DNMT3B, methyl CPG binding protein MeCP2 and histone deacetylase HDAC had no statistical significance mRNA expression content of the difference between the two groups (P > 0.05). In the male group only HAT1 of the relative expression of mRNA content in exposed group was higher than the control group, the differences were statistically significant (P < 0.001); in the female group and DNMT1mRNA the relative expression of HAT1mRNA in exposure group was significantly higher than the control group, with significant difference (P = 0.002,0.001), expression of other regulatory enzyme mRNA was not significant (P > 0.05).
[Conclusion]
1. styrene can cause workers such as cough, dizziness and other symptoms, and in acetone, thinners and other organic solvent under the action of the body will increase the degree of the reaction. The short period of workers exposed to styrene physical damage is not obvious, the damage effect remains to continue to observe.
2. styrene exposure has an effect on the micronucleus rate of human peripheral blood lymphocytes, and shows a certain genotoxic effect. Binuclear micronucleus can be used as an indicator of early genetic damage.
3. styrene exposure may induce gene expression regulation of enzyme DNMT1, the high expression of HMT and HAT1 mRNA in different degree, can be used as the genetic damage biomarkers of early, and regulate the expression of other genes enzymes DNMT3a, DNMT3b, MeCP2 and HDAC10 mRNA expression had no significant effect on.HAT1mRNA in male group styrene exposure, women groups the high expression of DNMT1mRNA in female styrene exposure high expression group, other regulatory enzymes such as DNMT3a, DNMT3b, HMT, MeCP2 and HDAC10 mRNA expression had no significant effect on gender differences in exposure group.

【學(xué)位授予單位】：濟南大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2012
【分類號】：R131

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