Similar carcinogenic effects in rats of 1-ethyl-1-nitroso-3-hydroxyethylurea and 1-hydroxyethyl-1-nitroso-3-ethylurea.

The two isomeric N-nitroso derivatives of the dialkylurea, 1-ethyl-3-(2-hydroxyethyl)urea, were given by gavage to 20 male F344 rats for 30 weeks at equimolar doses. The tumorigenic responses were compared with those to a similar dose of nitrosoethylurea or nitroso-2-hydroxyethylurea. Each of the nitrosomonoalkylureas caused death from tumors more rapidly than the analogous nitrosodialkylurea. Each of the nitrosodialkylureas induced a broader spectrum of tumors in the rats than did either nitrosoethylurea or nitroso-2-hydroxyethylurea, including neoplasms of the thyroid, lung, skin, colon, mesotheliomas and neoplasms of the brain and liver in high incidence, the last two of which were not seen in animals given the nitrosomonoalkylureas. On the other hand, there were fewer tumors of the forestomach in rats given the nitrosodialkylureas than with the nitrosomonoalkylureas. The major difference between 1-nitroso-1-ethyl-3-hydroxyethylurea and 1-nitroso-1-hydroxyethyl-3-ethylurea was that the former induced only neoplastic nodules in the liver of 30% of the rats, while the latter induced hepatocellular carcinomas in 55% of the rats; approximately half of the rats given either compound had brain neoplasms, which included astrocytomas, gliomas and oligodendrogliomas.