Induction of rat liver glutathione transferase isoenzyme 7-7 by lead nitrate.
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.
Dock
L
L
Institute of Environmental Medicine, Karolinska institutet, Stockholm, Sweden.
D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide / Q000378:metabolism; D000818:Animals; D003600:Cytosol / Q000187:drug effects / Q000201:enzymology; D004137:Dinitrochlorobenzene / Q000378:metabolism; D004790:Enzyme Induction / Q000187:drug effects; D004976:Ethacrynic Acid / Q000378:metabolism; D005982:Glutathione Transferase / Q000096:biosynthesis*; D066298:In Vitro Techniques; D007527:Isoenzymes / Q000096:biosynthesis*; D007854:Lead / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008115:Liver Regeneration; D008297:Male; D009566:Nitrates / Q000494:pharmacology*; D011506:Proteins / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D004137:Dinitrochlorobenzene; D007527:Isoenzymes; D009566:Nitrates; D011506:Proteins; D007854:Lead; D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide; C017461:lead nitrate; D005982:Glutathione Transferase; D004976:Ethacrynic Acid