癌变·畸变·突变 ›› 2017, Vol. 29 ›› Issue (6): 445-449.doi: 10.3969/j.issn.1004-616x.2017.06.008

• 论著 • 上一篇    下一篇

DEHP对3β-羟类固醇脱氢酶表达水平的影响

王利1,2, 彭鹏2,3, 徐新云2, 袁建辉2, 龙鼎新1   

  1. 1. 南华大学公共卫生学院, 湖南 衡阳 421001;
    2. 深圳市疾病预防控制中心毒理研究所, 广东 深圳 518055;
    3. 深圳大学生命科学学院, 广东 深圳 518060
  • 收稿日期:2017-03-23 修回日期:2017-09-26 出版日期:2017-11-30 发布日期:2017-11-30
  • 通讯作者: 徐新云,E-mail:xyxu2008@163.com E-mail:xyxu2008@163.com
  • 作者简介:王利,E-mail:478240233@qq.com。
  • 基金资助:
    深圳市科技研发基础研究项目(JCYJ20150402102135509,JCYJ20170306160553495)

Effects of di-(2-ethylhexyl) phthalate on expression of 3β-hydroxysteroid dehydrogenase

WANG Li1,2, PENG Peng2,3, XU Xinyun2, YUAN Jianhui2, LONG Dingxin1   

  1. 1. School of Public Health, South China University, Hengyang 421001, Hunan;
    2. Institue of Toxicology, Shenzhen Center for Disease Control and Prevention, Shenzhen 518055, Guangdong;
    3. School of Life Science, Shenzhen University, Shenzhen 518060, Guangdong, China
  • Received:2017-03-23 Revised:2017-09-26 Online:2017-11-30 Published:2017-11-30

摘要: 目的:研究邻苯二甲酸二(2-乙基己)酯(DEHP)对MCF-7细胞中3β-羟类固醇脱氢酶(3β-HSD)表达的影响。方法:采用不同浓度(0.05、0.1、0.2、0.4、0.8 mmol/L) DEHP对体外培养的MCF-7细胞分别染毒12、24和48 h,或同一浓度(0.8 mmol/L)染毒不同时间(3、6、12、24、48 h)后,荧光定量PCR检测各组MCF-7细胞3β-HSD mRNA表达水平,Western blot检测3β-HSD蛋白表达水平。结果:DEHP 0.1~0.8 mmol/L分别染毒细胞12~48 h,3β-HSD mRNA表达水平均较对照组升高,差异有统计学意义(P < 0.01);DEHP 0.05 mmol/L染毒细胞48 h,3β-HSD mRNA表达水平比对照组升高,差异有统计学意义(P < 0.05)。DEHP 0.8 mmol/L染毒细胞6~48 h,3β-HSD mRNA表达水平均较对照组升高,差异有统计学意义(P < 0.01)。DEHP 0.2~0.8 mmol/L染毒细胞24 h,3β-HSD蛋白表达水平较对照组升高,差异有统计学意义(P < 0.05或P < 0.01)。结论:DEHP可引起3β-HSD mRNA和蛋白表达水平升高,推测DEHP可能通过影响类固醇激素合成过程中3β-HSD表达水平的变化,从而产生生殖毒性作用。

关键词: 邻苯二甲酸二(2-乙基己)酯, 3β-羟基类固醇脱氢酶, 基因表达, 生殖毒性

Abstract: OBJECTIVE:To study the effects of di-(2-ethylhexyl) phthalate (DEHP) on expression of 3β-hydroxysteroid dehydrogenase (3β-HSD) in MCF-7 cells. METHODS:MCF-7 cells in cultured were exposed to DEHP in different doses (0.05,0.1,0.2,0.4,0.8 mmol/L) for 12,24,48 h,or to one dose (0.8 mmol/L) at different times (3,6,12,24,48 h). Expression of 3β-HSD mRNA was detected by real-time PCR,expression of 3β-HSD protein was detected by western blot. RESULTS:After treatment of MCF-7 cells with DEHP at 0.1-0.8 mmol/L for 12-48 h, expression levels of 3β-HSD mRNA were significantly higher than that of the control group (P < 0.01). Treatment with the lowest dose of DEHP treatment (0.05 mmol/L) for 48h also induced significant increase of 3β-HSD mRNA expression (P < 0.05). Our study also show a dose-effect relationship. Expression of 3β-HSD mRNA also showed time-dependent effects after treatment with 0.8 mmol/L DEHP for 6,12,24,48 h (P < 0.01). Expression of 3β-HSD protein was also higher after treatment with DEHP at doses of 0.2-0.8 mmol/L (P < 0.05 or P < 0.01). In the 0.4,0.8 mmol/L dose group,expression of 3β-HSD protein level increased gradually with the increasing doses (P < 0.05 or P < 0.01). CONCLUSION:DEHP induced up-regulation of 3β-HSD mRNA and protein. Our findings indicate that the mechanism of DEHP toxicity may be related to the induction of changes of 3β-HSD during steroid synthesis.

Key words: di-(2-ethylhexyl) phthalate, 3β-hydroxysteroid dehydrogenase, gene expression, reproductive toxicity

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