Modulation by benzo[a]pyrene of epidermal growth factor receptors, cell proliferation, and secretion of human chorionic gonadotropin in human placental cell lines.
Modulation by benzo[a]pyrene of epidermal growth factor receptors, cell proliferation, and secretion of human chorionic gonadotropin in human placental cell lines.
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DOI：
10.1016/0006-2952(95)00253-v
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发表时间：
1995-10
影响因子：
5.8
通讯作者：
Zhang Liyan;E. Connor;N. Chegini;K. Shiverick
中科院分区：
文献类型：
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作者：
Zhang Liyan;E. Connor;N. Chegini;K. Shiverick
临床观察表明，母亲吸烟对胎儿胎盘发育有显著的不利影响。本研究以人胎盘滋养层绒毛癌细胞系为研究对象，研究苯并[a]芘(BaP)对人胎盘滋养细胞生长因子受体(EGF)、细胞增殖和绒毛膜促性腺激素(HCG)分泌的影响。BaP对BeWo和JEG-3细胞的125I-EGF结合和EGF受体蛋白表达均有浓度依赖性的抑制作用。然而，BaP对两种细胞的EGF受体mRNA的稳态表达水平均无显著影响。在有血清的条件下，10和50μM BaP对细胞增殖无影响或略有增加，而在无血清条件下，细胞的增殖逐渐减弱。BaP可抑制EGF对两种细胞的促有丝分裂作用。对滋养层细胞内分泌功能的进一步研究表明，BaP对BeWo细胞的基础hCG分泌和EGF刺激的hCG分泌均显著减少，而对JEG-3细胞未见不良影响。BaP对两种细胞系的细胞色素P450 1A1均有浓度依赖性的诱导作用。因此，研究表明BaP介导的EGF受体缺失改变了滋养层细胞的增殖和内分泌功能，并且可能涉及不同的机制来调节BeWo和JEG-3细胞的hCG分泌。此外，本研究支持利用BeWo和JEG-3滋养细胞系研究胎盘毒性的生物标志物和机制的可行性。
Clinical observations indicate that maternal cigarette smoking has significant detrimental effects on fetoplacental development. The present study used human trophoblastic choriocarcinoma cell lines of placental origin to investigate the effects of benzo[a]pyrene (BaP) on epidermal growth factor (EGF) receptors, cell proliferation and human chorionic gonadotropin (hCG) secretion. BaP decreased125I-EGF binding and EGF receptor protein in a concentration-related manner in both BeWo and JEG-3 cell lines. The steady-state level of EGF receptor mRNA, however, was not changed significantly by BaP in either cell line. Cell proliferation was unchanged or slightly increased following exposure to 10 and 50 μM BaP in the presence of serum, whereas proliferation progressively decreased in cells exposed under serum-free conditions. The mitogenic effect of EGF was inhibited by cotreatment with BaP in both cell lines. Further study of trophoblast endocrine function showed that both basal and EGF-stimulated secretion of hCG was reduced significantly by BaP exposure in BeWo cells, whereas no adverse effect was seen in JEG-3 cells. Finally, cytochrome P450 1A1 (CYP1A1) was induced in a concentration-dependent manner by BaP in both cell lines. Thus, data indicate that the BaP-mediated loss of EGF receptors alters trophoblast proliferation and endocrine function, and that different mechanisms may be involved in the regulation of hCG secretion in BeWo and JEG-3 cells. In addition, this study supports the feasibility of using the BeWo and JEG-3 trophoblastic choriocarcinoma cell lines to investigate biomarkers and mechanisms of placental toxicity.