Zhang L, Shiverick K T
Department of Pharmacology and Therapeutics, College of Medicine, University of Florida, Gainesville 32610-0267, USA.
Biochem Biophys Res Commun. 1997 Feb 3;231(1):117-20. doi: 10.1006/bbrc.1997.6053.
This study compared the effects of benzo(a)pyrene (BaP) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), two aryl hydrocarbon receptor (AhR) agonists, on proliferation and gene expression in the human placental choriocarcinoma JEG-3 cell line. BaP significantly inhibited [3H]thymidine incorporation, whereas no effect of TCDD was observed over a 7 day period. TCDD and BaP both showed induction of cytochrome P450 1A1 (CYP1A1), whereas only BaP caused a significant loss of EGFRs. Exposure to 10 microM BaP significantly increased the steady state mRNA level of transforming growth factor (TGF)-beta 1, while the c-myc mRNA levels were decreased by 61%. In contrast, TCDD showed no changes in mRNA levels for TGF-beta 1 and c-myc. Thus, although both compounds induce CYP1A1, only BaP inhibits cell proliferation which is correlated with disruption of expression of significant regulators of trophoblast growth.
本研究比较了两种芳烃受体（AhR）激动剂苯并（a）芘（BaP）和2,3,7,8-四氯二苯并对二恶英（TCDD）对人胎盘绒毛膜癌细胞系JEG-3细胞增殖和基因表达的影响。BaP显著抑制[3H]胸腺嘧啶核苷掺入，而在7天的时间内未观察到TCDD有此作用。TCDD和BaP均显示出细胞色素P450 1A1（CYP1A1）的诱导，而只有BaP导致表皮生长因子受体（EGFRs）显著减少。暴露于10微摩尔BaP显著增加了转化生长因子（TGF）-β1的稳态mRNA水平，而c-myc mRNA水平下降了61%。相反，TCDD对TGF-β1和c-myc的mRNA水平没有影响。因此，尽管两种化合物都诱导CYP1A1，但只有BaP抑制细胞增殖，这与滋养层生长的重要调节因子表达的破坏有关。
