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苯并(a)芘对H1299细胞CYP1A1酶活力和相关基因表达的影响
  • ISSN号:1002-3127
  • 期刊名称:《毒理学杂志》
  • 时间:0
  • 分类:X503.1[环境科学与工程—环境工程]
  • 作者机构:[1]劳动卫生与环境卫生学系, [2]环境与健康教育部重点实验室,武汉430030
  • 相关基金:国家自然科学基金项目(30671735)
中文摘要:

背景与目的:研究p63与p73的mRNA表达与BaP致人肺腺癌细胞(H1299)和人支气管上皮细胞(16HBE)DNA损伤的关系。材料与方法:分别用不同浓度BaP(8、16、32、64和128μmol/L)处理H1299和16HBE两种细胞,在4 h和12 h时,使用相应的生化检测试剂盒分别测定细胞裂解液中MDA的水平和SOD、GSH-Px的活性,用qRT-PCR方法测定处理后细胞的p53、p63、p73、mdm2和mdm4的mRNA水平;用Comet实验评价细胞DNA损伤程度。结果:16、32和64μmol/L BaP处理4 h时,两种细胞MDA水平显著性升高,SOD和GSH-Px活性显著性下降(P〈0.05)。用BaP处理H1299和16HBE细胞4 h和12 h时均观察到DNA损伤随浓度增加而加重,且呈剂量-效应关系(P〈0.01),mdm2、mdm4mRNA表达水平升高(P〈0.01)。不过仅在12 h时p53基因mRNA表达水平较对照组显著增加(P〈0.01)。在4 h和12 h时点,仅在H1299细胞的p63和p73mRNA表达增加(P〈0.05)。结论:在BaP致p53缺失的H1299细胞的DNA损伤中,BaP可能通过不依赖p53信号通路激活了p63和p73 mRNA的表达。

英文摘要:

BACKGROUND AND AIM: The associations between the changes of p63 and p73 in mRNA levels and the BaP-induced DNA damage in H1299 cells and in 16HBE cells were investigated. MATERIALS AND METHODS: Both H1299 cells and 16HBE cells were treated with BaP at various concentrations (8, 16, 32, 64 and 128 μmol/L) for 4 h and 12 h.At the two time points, the levels of MDA,SOD and GSH-Px were measured using the test kits. The mRNA levels of p53,p63,p73,mdm2 and mdm4 genes were detected by RT-PCR assay. DNA damage in the cells were evaluated by Comet assay. RESULTS: At 4 h, enhanced MDA level was observed (P 〈 0.05) . However, levels of SOD and GSH-Px were significantly decreased(P 〈 0.05 for both) in both kinds of cells. After 16HBE and H1299 cells were treated for 4 h and 12 h, DNA damage and mRNA expression levels of mdm2 and mdm4 genes increased in a dose-dependent manner(P 〈 0.01 for all) . But enhanced mRNA expression level of p53 was observed only at 12 h(P 〈 0.01) In addition,significant up-regulation of p63 and p73 genes in mRNA levels at the two time points were observed in H1299 cells( P 〈 0.05) . CONCLUSION: The BaP-induced DNA damage may be associated with enhanced mRNA levels of p63 and p73 genes in the p53-null H1299 cells.

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期刊信息
  • 《毒理学杂志》
  • 中国科技核心期刊
  • 主管单位:北京市卫生和计划生育委员会
  • 主办单位:北京市预防医学研究中心 北京大学医学部公共卫生学院
  • 主编:高星
  • 地址:北京市东城区和平里中街16号
  • 邮编:100013
  • 邮箱:dulixuezz@163.com
  • 电话:010-64407284
  • 国际标准刊号:ISSN:1002-3127
  • 国内统一刊号:ISSN:11-5263/R
  • 邮发代号:82-178
  • 获奖情况:
  • 国内外数据库收录:
  • 美国化学文摘(网络版),日本日本科学技术振兴机构数据库,中国中国科技核心期刊,中国北大核心期刊(2008版),中国北大核心期刊(2011版),中国北大核心期刊(2014版)
  • 被引量:4872