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应用gpt delta转基因小鼠模型评价电子烟气溶胶的遗传毒性 被引量:1

Evaluation of genotoxicity of e-cigarette aerosol using gpt delta transgenic mouse model
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摘要 为评价电子烟气溶胶的遗传毒性,采用gpt delta转基因小鼠模型,以外周血网织红细胞为材料,通过微核试验检测电子烟气溶胶造成的染色体损伤作用,Pig-a基因突变试验检测电子烟气溶胶的致突变作用;以肺组织为材料,通过实时荧光定量PCR检测电子烟气溶胶对mmu-miR-34a、mmu-let-7a、Akt1、Il-6和Tnf-a基因表达的影响。结果表明:与对照组相比,电子烟气溶胶低、高剂量组和3R4F参比卷烟烟气低、高剂量组的微核率、Pig-a基因突变频率和网织红细胞百分比(RET%)差异均无统计学意义(P>0.05)。电子烟气溶胶低、高剂量组中mmu-miR-34a、Il-6和Tnf-a的表达均显著降低(P<0.05),电子烟气溶胶高剂量组中mmu-let-7a的表达升高(P<0.05)。3R4F参比卷烟烟气高剂量组中mmu-miR-34a、mmu-let-7a和Tnf-a的表达均显著降低(P<0.05)。未检出电子烟气溶胶对gpt delta转基因小鼠有显著遗传毒性,但发现电子烟气溶胶显著影响DNA损伤和炎症相关基因的mRNA表达。 In this study, gpt transgenic mouse model was used to evaluate the genotoxicity of e-cigarette aerosol. Taking peripheral blood reticulocytes as experimental assay, the effects of e-cigarette aerosol on chromosome damage were detected by micronucleus test, and the mutagenic effect of e-cigarette aerosol was detected by Pig-a gene mutation test. Using lung tissue as experimental assay, the effects of e-cigarette aerosol on the gene expression of mmu-miR-34a, mmu-let-7a, Akt1, Il-6 and Tnf-a were detected by real-time fluorescent quantitative PCR. The results showed that comparing with the control group, micronucleus frequency, Pig-a mutation frequency and RET% were not significantly different in the low- and high-dose e-cigarette aerosol group and the low- and high-dose group of 3R4F reference cigarette smoke (P>0.05). The mmu-miR-34a, Il-6 and Tnf-a in the low- and high-dose groups of e-cigarette aerosol significantly decreased (P< 0.05), and the expression of mmu-let-7a increased (P<0.05) in the high-dose group. The mmu-miR-34a, mmu-let-7a and Tnf-a in the high-dose group of 3R4F reference cigarette smoke significantly reduced (P< 0.05).In conclusion, the genotoxicity of e-cigarette aerosol could not be detected in gpt delta transgenic mice model, however e-cigarette aerosol significantly affected the mRNA expression of DNA damage and inflammation- related genes.
作者 管莹 许亮 尤馨悦 高茜 唐伟锋 米其利 曹易懿 朱洲海 奚晶 刘维映 栾洋 夭建华 GUAN Ying;XU Liang;YOU Xinyue;GAO Qian;TANG Weifeng;MI Qili;CAO Yiyi;ZHU Zhouhai;XI Jing;LIU Weiying;LUAN Yang;YAO Jianhua(Key Laboratory of Tobacco Chemistry of Yunnan, Technology Center of China Tobacco Yunnan Industrial Co., Ltd., Kunming 650231, China;Hongqiao International Institute of Medicine, School of Public Health, School of Medicine, Shanghai Jiao Tong University, Shanghai 200025, China;Shanghai Integrated Biotech Solutions Co., Ltd., Shanghai 201203, China;Institute of Environmental Pollution and Health, School of Environmental and Chemical Engineering, Shanghai University, Shanghai 200444, China)
出处 《烟草科技》 EI CAS CSCD 北大核心 2019年第4期51-56,共6页 Tobacco Science & Technology
基金 中国烟草总公司重大专项项目"电子烟溶剂雾化吸入安全风险评估研究"[110201501002(XX-02)] 云南中烟工业有限责任公司科技项目"电子烟安全风险体外毒理学评价方法研究"(2016JC01) 云南省烟草化学重点实验室开放基金项目"应用gpt delta转基因小鼠模型评价电子烟的遗传毒性"(20165392003401288)
关键词 gptdelta转基因小鼠 电子烟 气溶胶 遗传毒性 Pig-a基因 突变 gpt delta transgenic mice E-cigarette Aerosol Genotoxicity Pig-a gene Mutation
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