Two nitrosated bile acid conjugates, N-nitrosoglycocholic acid and N-nitrosotaurocholic acid, were examined for carcinogenicity in a 2-year study with male Fischer rats using a 6-week p.o. dosing protocol with a total of 300 mg compound/rat. Both compounds were approximately equally carcinogenic and induced significant levels of hepatocellular carcinoma in 54 to 70% of the animals at risk. Gastric tumors of the glandular and aglandular stomach were observed in 12 to 13% of the treated rats. Although the incidence was not significant, these levels were much higher than those in historic controls. Malignant liver and gastric tumors were not detected in vehicle control rats. Alkaline phosphatase-positive foci, putative early mucosal alterations which may precede neoplasia, were found in approximately 35% of the glandular stomachs of compound-treated rats but not in those of control rats.
This work was supported by National Institute of Environmental Health Sciences Grant 5-PO1-ES00597.