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 six months in a high dose group which received 1 mmole MNCO/kg IP weekly for 6 months and to 1 year in a group which received 0.33 mmole/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 IP injection of 3 mmoles/kg although this dose caused no deaths acutely.