Induction of tumors in the liver, urinary bladder, esophagus and forestomach by short-term treatment with different doses of N,N'-dibutylnitrosamine in rats.

Abstract

The multipotential carcinogen N,N'-dibutylnitrosamine (DBN) was given to F344 male rats for 2 weeks at three dose levels to study the concentration dependence of its organ specificity. Groups of 20 rats were given water containing 0.25, 0.125 or 0.063% DBN for 2 weeks and then tap water only to drink until they were killed 52 weeks after the start of the experiment. DBN induced preneoplastic lesions in the liver, esophagus, forestomach and urinary bladder. Carcinoma was found only in the liver. Induction of preneoplastic focal hepatocyte lesions positive for the P-form of glutathione S-transferase (GST-P) was quantitatively dependent on the dose of DBN. In the urinary bladder, the incidences of papillary or nodular hyperplasia (PNH) and papilloma of transitional cells tended to increase at higher doses. The incidence and number per unit length of basal cell-type hyperplasias of the esophageal epithelium were significantly higher in all DBN groups than in the control group, through the increase did not show a clear dose-dependency. The incidence of epithelial basal cell hyperplasia of the forestomach was significantly increased at all doses and the increase was apparently dose-related. These results indicate that even in a short-term experiment, DBN exerted multipotential carcinogenic effects. Thus, this system could be used for assay of the modifying effects of compounds administered subsequently on carcinogenesis in different organs.