莠去津诱导大鼠肝 P-糖蛋白、谷胱甘肽 S-转移酶和细胞色素 P450 的表达。

Induction of P-glycoprotein, glutathione-S-transferase and cytochrome P450 in rat liver by atrazine.

机构信息

Tissue Engineering Research Center, AIST, METI, 1-8-31 Midorigaoka, Ikeda, Osaka 563-8577, Japan.

出版信息

Environ Toxicol Pharmacol. 2002 Aug;12(1):1-6. doi: 10.1016/s1382-6689(01)00121-1.

Abstract

We studied the effects of intraperitoneally administered atrazine on two hepatic neoplastic markers, P-glycoprotein (P-gp), and glutathione-S-transferase (GST), and several phase I drug-metabolizing enzyme cytochrome P450 (CYP) subfamilies in hepatic microsomes and cytosol of Fischer rats. The P-gp content was increased after 24 h of atrazine administration at 50 mg/kg, and maximum P-gp induction was observed at 300 mg/kg for 3 days. GST-P was induced at a lower dose than P-gp, from 10 mg/kg, but no other form of GST, such as GST1A1, was induced by the same dose. Among the CYP families, CYP1A2 was highly and CYP2B was slightly induced by atrazine while the CYP3A content remained unchanged. The liver plasma membrane marker alkaline phosphatase (AP) was not induced by the same doses. The inductions of P-gp, GST-P and CYP1A2 observed may explain some of the reported tumor-promoting properties and toxicity of atrazine in vivo.

摘要

我们研究了腹腔内给予莠去津对两种肝肿瘤标志物，P-糖蛋白（P-gp）和谷胱甘肽-S-转移酶（GST），以及肝微粒体和胞浆中几种 I 相药物代谢酶细胞色素 P450（CYP）亚家族的影响。在给予 50mg/kg 莠去津 24 小时后，P-gp 含量增加，在给予 300mg/kg 莠去津 3 天时，P-gp 诱导达到最大值。GST-P 的诱导剂量低于 P-gp，从 10mg/kg 开始，但同一剂量没有诱导其他形式的 GST，如 GST1A1。在 CYP 家族中，CYP1A2 被莠去津高度诱导，而 CYP2B 则被轻度诱导，而 CYP3A 的含量保持不变。同样剂量的肝质膜标记物碱性磷酸酶（AP）没有被诱导。观察到的 P-gp、GST-P 和 CYP1A2 的诱导可能解释了莠去津在体内的一些报道的促瘤特性和毒性。