2002-ETP-cytochrome P450 in rat liver by atrazine(前言选用,大鼠&P450).pdf

Environmental Toxicology and Pharmacology 12 (2002) 1–6 /locate/etap Induction of P-glycoprotein, glutathione-S-transferase and cytochrome P450 in rat liver by atrazine M. Omedul Islam, Masayuki Hara *, Jun Miyake Tissue Engineering Research Center, AIST, METI, 1-8-31 Midorigaoka, Ikeda, Osaka 563-8577, Japan Received 7 June 2001; received in revised form 19 November 2001; accepted 21 November 2001 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. © 2002 Elsevier Science B.V. All rights reserved. Keywords: Atrazine; P-glycoprotein; Glutathione-S-transferase; Placental form; Cytochrome P450; Rat 1. Introduction 1987). It has been report