Inhibition by 3-amino-1H-1,2,4-triazole of hepatic tumorigenesis induced by diethylstilbestrol alone or combined with N-nitrosobutylurea in WF rats.

Six groups of inbred male WF rats were castrated at 40 days of age. Group 1 was given no further treatment; groups 3-6 received sc implantations of 5.0 mg diethylstilbestrol [(DES) CAS: 56-53-1]. At 50-55 days of age, groups 5 and 6 were given drinking water containing 5.0 mg N-nitrosobutylurea [(NBU) CAS: 869-01-2] per day for 30 days. After the termination of NBU treatment, groups 2, 4, and 6 were given 3-amino-1H-1,2,4-triazole (AT), considered an inhibitor of hydroperoxidases, in the drinking water throughout the experiment. Castrated male rats or rats castrated and treated with AT alone developed neither hepatic tumors nor pituitary tumors. The hepatic tumor incidence, the size and total number of hepatic tumors, and the mean liver weight were significantly reduced in rats given the DES-NBU combination and slightly reduced in rats given DES alone when AT was administered. In contrast, AT treatment did not change the pituitary tumor incidence and the mean pituitary weight. The thyroid gland weights were approximately 7-44 times greater in AT-treated groups than those in each corresponding control group. These data indicate that AT inhibited hepatic but not pituitary tumorigenesis and caused enlargement of the thyroid gland. The present study, therefore, provides evidence that the metabolic activation of DES by oxidation is involved in rat liver carcinogenesis.