Carcinogenicity of 1-(2-hydroxyethyl)-1-nitrosourea and 3-nitroso-2-oxazolidinone administered in drinking water to male MRC-Wistar rats: induction of bone, hematopoietic, intestinal, and liver tumors

Abstract

A previous report was made on the carcinogenicity of 1-(2-hydroxyethyl)-1-nitrosourea [(HENU) CAS: 13743-07-2] in rats. Because the cyclic nitrosocarbamate 3-nitroso-2-oxazolidinone (NOZ) is readily produced during the synthesis of HENU and can be confused with HENU, HENU was retested and NOZ was tested for carcinogenicity. Improved syntheses of both compounds are described. They were administered in drinking water to male MRC-Wistar rats for 1 year, starting at 3 or 9 weeks of age. The HENU-treated rats showed incidences of 48% for bone tumors, 32% for intestinal tumors (mostly duodenal adenocarcinomas), and 53% for lymphoma-leukemia. Of the bone tumors, which were evaluated microscopically and radiologically, 68% were osteosarcomas and 32% were osteoblastomas. The skeletal distribution of these tumors was similar to that of human osteosarcoma, with the tumors occurring most frequently in the lower limbs near the knees. Of the hematopoietic tumors, the majority were lymphoblastic lymphoma-leukemia, which showed a diffuse organ distribution resembling human B-cell (Burkitt's-like) lymphoblastic lymphoma-leukemia, and differed from the usual type of convoluted T-cell lymphoma-leukemia induced by other nitrosoureas in rats and mice. NOZ induced intestinal tumors (mostly duodenal adenocarcinomas) in 80% and liver tumors (mostly hepatocellular adenomas) in 53% of the rats.