gamma-Glutamyltranspeptidase-conferred resistance to hydroquinone induced GSH depletion and toxicity in isolated hepatocytes.
Hepatocyte resistance against glutathione (GSH) depleting xenobiotics was studied in an in vitro model. Hepatocytes were isolated from carcinogen treated rats that had received phenobarbital for three weeks. Isolated cells were incubated in GSH containing buffer with hydroquinone, which depleted GSH. Cells were then seeded on collagen coated plates and cultured overnight in complete medium. Attached cells were stained and the proportion of gamma-glutamyltranspeptidase (GGT)-positive cells was counted. It was found that toxicity related to GSH depletion increased the proportion of GGT-positive cells from 10-15% up to 40-60%, indicating that the toxicity mainly affected GGT-negative cells. GSH added to the buffer was essential for this effect. It is concluded that GGT may protect GGT-positive hepatocytes from GSH depletion and toxicity early during liver carcinogenesis.
D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004052:Diethylnitrosamine / Q000494:pharmacology; D004351:Drug Resistance; D005978:Glutathione / Q000378:metabolism*; D006873:Hydroquinones / Q000633:toxicity*; D066298:In Vitro Techniques; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008715:Methionine / Q000494:pharmacology; D010634:Phenobarbital / Q000494:pharmacology; D051381:Rats; D005723:gamma-Glutamyltransferase / Q000378:metabolism*
D006873:Hydroquinones; D004052:Diethylnitrosamine; D008715:Methionine; D005723:gamma-Glutamyltransferase; D005978:Glutathione; C031927:hydroquinone; D010634:Phenobarbital