Induction of preneoplastic and neoplastic lesions in rats treated N-nitroso compounds

Dose-related changes of incidences of pre-neoplastic and neoplastic lesions in the liver or urinary bladder were examined with N-nitroso-dimethylamine (NDMA) or N-nitrosobutyl-4-hydroxybutylamine (NBHA) respectively. The incidences of lesions by the two carcinogens were compared in short-term and long-term experiments. In a short-term experiment, rats were given a basal diet containing NDMA at concentrations of 10.0, 1.0 and 0.1 mg/kg for 6 weeks, after initiation by a single i.p. injection of N-nitrosodiethylamine (NDEA). Similar, long-term experiments (96 weeks) were also performed, but without NDEA pretreatment. A clear dose-related effect was found in the induction of pre-neoplastic lesions when the groups given 10.0 and 1.0 mg/kg NDMA were compared. This coincided with the results of a long-term experiment on the induction of hyperplastic nodules and hepatocellular carcinomas. Various concentrations of 0.05 to 0.005% of NBHA in the drinking water were given for different periods up to 12 weeks, in a short-term, and up to 40 weeks in a long-term experiment. Incidences of early preneoplastic lesions of the cell surface observed by scanning electron microscopy showed a tendency to increase with longer duration and higher dose (0.01 to 0.05%). A clear dose-dependent effect was found for the incidence of papilloma and carcinoma in the groups subjected to longer treatments.