Induction of rat liver glutathione transferase isoenzyme 7-7 by lead nitrate

Abstract

The glutathione transferase (GST) activity of rat liver cytosolic preparations with ethacrynic acid (EA) and (+/-)-7 beta, 8 alpha-dihydroxy-9 alpha, 10 alpha-epoxy-7,8,9,10-tetrahydro-benzo(a)pyrene (BPDE) as substrates, increased by 125 and 350%, respectively, in animals that had been treated with a single intravenous dose of Pb(NO3)2 (100 mumol/kg body wt) 48 h prior to sacrifice, whereas activity with 1-chloro-2,4-dinitrobenzene (CDNB) increased only about 60%. No induction of these activities was observed in cytosolic preparations from regenerating rat liver, whereas cytosols prepared from hepatocyte nodules showed increased activity with all three substrates (EA: 400%; BPDE: 790%; CDNB: 205%). These results suggest that Pb(NO3)2 is an inducer of GST 7-7, an isoenzyme that has been associated with hepatocarcinogenesis. Elucidation of the mechanism of GST 7-7 induction by lead may contribute to our understanding of the process of chemical carcinogenesis.