【摘 要】
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Benzene has been an environmental and industrial pollutant which is widely utilized in various applications.At present, apoptosis is regarded as a toxic mechanism of hematotoxicity triggered by benzen
【机 构】
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Department of Occupational Health and Environmental Health, School of Public Health, Capital Medical
【出 处】
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2016(第二届)毒性测试替代方法与转化毒理学(国际)学术研讨会暨有害结局路径(AOP)与风险评估培训会议
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Benzene has been an environmental and industrial pollutant which is widely utilized in various applications.At present, apoptosis is regarded as a toxic mechanism of hematotoxicity triggered by benzene, but the influence of miRNAs on benzene-induced apoptosis still remain unclear.In a population-based study, benzene-exposed group recruit workers whose concentration of air benzene was 3.50±1.60 mg/m3, and control workers who exposed to 0.06±0.01 mg/m3 air benzene concentration.Quantitative analysis were performed for miR-133a and pro-apoptotic genes Caspase-3 and Caspase-9 expression using qRT-PCR.Further, the correlation between miR-133a and pro-apoptotic genes was analyzed by Pearson correlation analysis and multiple linear regression.In vitro, we explored the activation of apoptosis induced by benzene metabolites (1,4-Benzoquinone, PBQ) via AO/EB staining and TEM ultrastructural analysis.Additionally, the underlying mechanism of PBQ-induced apoptosis was performed using lentivirus vectors transfection.In population-based study, Caspase-9 and Caspase-3 was upregulated while miR-133a expression decreased in benzene-exposed group.We also found that miR-133a was reversely correlated with Caspase-9 expression, and Caspase-9 expression was positively associated with Caspase-3 expression.The results indicated that miR-133a was significantly associated with apoptosis induced by benzene metabolites.In vitro, the results demonstrated that PBQ induced apoptosis evidently.Meanwhile, PBQ decreased miR-133a expression and increased pro-apoptotic genes (Caspase-9 and Caspase-3) expression in a dose-dependent manner.Finally, over-expression of miR-133a attenuated PBQ-induced apoptosis by targetly decreasing Caspase-9 expression.In conclusion, our data indicated that benzene induced hematotoxicity by decreasing miR-133a and upregulating Caspase-9 which enhanced apoptosis generation.
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