Activation by Chemical Carcinogens of γ-Glutamyl Transpeptidase in Rat and Mouse Liver 2

Feeding a diet containing carcinogenic 3′-methyl-4-dimethylaminoazobenzene (3′-MeDAB), 2-acetylaminofluorene (2-AAF), thioacetamide, DL-ethionine or administering dimethylnitrosamine in drinking water gradually increased γ-glutamyl transpeptidase (glutathionase) in rat liver. A single large dose of strong hepatocarcinogens such as dimethylnitrosamine, 2-AAF, or 3′-Me-DAB led to higher levels of glutathionase within 24–48 hours. Diet containing carcinogenic o-aminoazotoluene (o-AAT) also activated glutathionase gradually in mouse liver. Continuous feeding of diet containing the noncarcinogenic 2-methyl-4-dimethylaminoazobenzene caused only a temporary increase of glutathionase. Hypophysectomy inhibited the activation of glutathionase in liver of rats fed 3′-Me-DAB or 2-AAF. For 70 and 110 days, respectively, the increased activity of glutathionase depended on the continued administration of 3′-MeDAB or dimethylnitrosamine. After these periods, high glutathionase activity in rat liver became a permanent feature independent of further carcinogen. The results suggest that the activation of glutathionase in rat liver is related, almost from the beginning, to the carcinogenic process induced by chemical compounds.