CARCINOGENICITY IN RATS OF THE NITROSOUREA AMINO-ACID N-DELTA-(N-METHYL-N-NITROSOCARBAMOYL-L-ORNITHINE

Abstract

The carcinogenicity of the nitrosourea amino acid, N.delta.-(N-methyl-N-nitrosocarbamoyl)-L-ornithine (MNCO), and its acute cytotoxicity were studied in Wistar rats. MNCO treatment induced a high incidence of neoplasms in breast, kidney and skin and a lower incidence of tumors in the exocrine pancreas and ear duct. The duration of these studies was limited by toxicity and carcinogenicity to 6 mo. in a high dose group which received 1 mmol MNCO/kg i.p. weekly for 6 mo. and to 1 yr in a group which received 0.33 mmol/kg. In the latter group the incidence of neoplasms was breast, 40%; skin, 52%; kidney, 81%; pancreas, 19%; and ear duct, 4%. All pancreases in this group also contained foci of fibrosis and cyst formation, and atypical acinar cell nodules. Acute cytotoxic effects were noted in pancreas, kidney and skin after a single i.p. injection of 3 mmol/kg although this dose caused no deaths acutely.