草鱼肝细胞中诱导剂对EROD作用的剂量效应研究

Research on dose-response of inducers to effect on EROD in grass carp hepatocyte

在研究GCL细胞中EROD催化底物反应时间的基础上分别以三种数学模型拟合,分析比较了诱导剂TCDD、PCB、PB、BaP、3-MC、BNF对GCL细胞EROD酶活的剂量-效应曲线,结果表明Log-Normal模型能较好的拟合药酶诱导前升后降的钟形效应曲线,所得方程参数值p100和EC100可用于药物代谢酶的诱导研究;Gentox模型拟合度相对较低且其EC50值显著高于半效应浓度;Logistic模型只能拟合曲线诱导上升部分而且EC50和p100与Log-Normal模型相比显著偏高。进一步研究结果显示诱导剂TCDD对GCL细胞作用时间越长,EC100越大,p100越小,但在作用48h后即达到较大诱导效应,延长时间并无显著加强作用。

EROD activity could been induced by some hydrocarbons, especially polyaromatic hydrocarbons, so EROD had already been used as an ecotoxicological indicator of aromatic pollutant in water environment. In this paper, the dose-response of EROD induction was explored by three mathematics modules in grass carp bepatocyte. Firstly the time of ERF metabolism catalyzed by EROD in GCL cell lines was optimized to 60 min. In such condition, dose-response curves of TCDD, PCB, PB, BaP, 3-MC and BNF to induce EROD activity fitted by Log-Normal, Gentox and Logistic modules were conapared. Log-Normal module could fit the bell-shape curves well and its parameters P100 and ECIoo were useful to investigate induction of biotransformation enzyme. Gentox＇ s fitness was less than other two modules＇ and its EC50 values were higher than half-response doses remarkably. Logistic module could only fit curves in ascending phase and its P100 and EC50 were higher than Log-Nonnal＇s remarkably. Further study showed that EC50 increased and P100 descended significantly while the exposure time to TCDD extended from 12 h to 48 h. Above was preparatory research to establish a fish cell model of induced drug-metabolizing enzyme which was significant to clarify the metabolizing mechanism of fishery medicine.