Zhang L, Connor E E, Chegini N, Shiverick K T
Department of Pharmacology and Therapeutics, College of Medicine, University of Florida, Gainesville 32610, USA.
Biochem Pharmacol. 1995 Oct 12;50(8):1171-80. doi: 10.1016/0006-2952(95)00253-v.
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 benz[a]pyrene (BaP) on epidermal growth factor (EGF) receptors, cell proliferation and human chorionic gonadotropin (hCG) secretion. BaP decreased 125I-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 microM 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.
临床观察表明，母亲吸烟对胎儿胎盘发育有显著的有害影响。本研究使用胎盘来源的人滋养层绒毛膜癌细胞系，研究苯并[a]芘（BaP）对表皮生长因子（EGF）受体、细胞增殖和人绒毛膜促性腺激素（hCG）分泌的影响。在BeWo和JEG-3细胞系中，BaP均以浓度相关的方式降低了125I-EGF结合和EGF受体蛋白。然而，在任一细胞系中，BaP均未显著改变EGF受体mRNA的稳态水平。在有血清存在的情况下，暴露于10和50 microM BaP后，细胞增殖未发生变化或略有增加，而在无血清条件下暴露的细胞中，增殖逐渐降低。在两个细胞系中，BaP与EGF共同处理均抑制了EGF的促有丝分裂作用。对滋养层内分泌功能的进一步研究表明，在BeWo细胞中，BaP暴露显著降低了hCG的基础分泌和EGF刺激的分泌，而在JEG-3细胞中未观察到不良影响。最后，在两个细胞系中，BaP均以浓度依赖的方式诱导细胞色素P450 1A1（CYP1A1）。因此，数据表明，BaP介导的EGF受体丧失改变了滋养层细胞的增殖和内分泌功能，并且BeWo和JEG-3细胞中hCG分泌的调节可能涉及不同的机制。此外，本研究支持使用BeWo和JEG-3滋养层绒毛膜癌细胞系研究胎盘毒性的生物标志物和机制的可行性。
