Decreased induction of gamma-glutamyltransferase activity by 3'-methyl-4-dimethylaminoazobenzene in the liver of rats given carcinogen-containing diet for several generations.

gamma-Glutamyltransferase (G-GT) has been widely used as a marker of the preneoplastic stage of chemical carcinogenesis. We obtained male rats of Donryu strain that showed a reduced response to 3'-methyl-4-dimethylaminoazobenzene (3'-MeDAB) in terms of induction of G-GT activity in the liver, by giving rats of this strain diet containing the carcinogen for several generations. In these animals, hepatic G-GT activity was only slightly higher than normal even after more than 20 weeks of continuous post-weaning exposure to the carcinogen, and it decreased to below the normal level if administration of the carcinogen was discontinued. In normal male rats, administration of diet containing 3'-MeDAB for more than 2 weeks resulted in an increase in hepatic G-GT activity, and the activity was increased further by a single injection of hydrocortisone. This response to glucocorticoid was also lost in "3'-MeDAB-resistant rats." Transient elevation of fetal hepatic G-GT activity occurred at the end of gestation of "resistant rats" as well as normal rats, but the highest activity at birth of the "resistant rats" was significantly lower than that of normal rats. We observed retardation of tumor development in the liver of fourth and fifth generation rats maintained continuously on diet containing 3'-MeDAB.