Alteration in glutathione level during carcinogenesis of hamster buccal pouch mucosa

Abstract

This study examined the level of glutathione (GSH)--a tripeptide that may have an important role in detoxification of carcinogens--in the hamster buccal pouch mucosa (HBPM) by a 12-week regimen of tri-weekly topical application of 7,12-dimethylbenz[a]anthracene (DMBA) in mineral oil. GSH was quantified periodically and shown to be doubled in carcinogen-treated vs. control pouch mucosa. In the tumors that developed, the level of GSH was three times that of the controls. Previous studies showed that gamma-glutamyl transpeptidase (GGT), one of the enzymes that may be responsible for the detoxification of carcinogens, was increased in the hamster mucosa pre-neoplastic foci, but decreased with the formation of overt neoplasia. GGT and GSH are intimately related, since GGT is the only enzyme that can cleave the intact GSH molecule. The increase in both GSH and GGT levels may be responsible for the increased resistance of the pre-neoplastic pouch epithelium to the toxic effects of the carcinogen.