Similar Carcinogenic Actions of Nitrosoalkylureas of Varying Structure Given to Rats by Gavage

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Abstract
To relate the tumorigenic effects of directly acting alkylating nitrosoalkylureas to their chemical structure, a series of these compounds was given to F344 rats by gavage at approximately equimolar doses. In some cases, more than one dose rate was used. Potency, as measured by time to death with tumors, was similar for nitrosomethylurea and nitrosoethylurea, although the tumor pattern was different between the two. Nitrosoallylurea was of similar potency, and induced a spectrum of tumors similar to nitrosoethylurea. Nitroso-n-butyl-, n-amyl- and n-hexyl-ureas were less potent than nitrosoethylurea, but induced a similar pattern of tumors. All of the nitrosoureas induced tumors of the forestomach, usually in high incidence, except nitroso-2-hydroxypropylurea, which caused death of the rats with thymic lymphoma within 6 months. Nitroso-3-hydroxypropylurea was much less potent than its 2-isomer, but induced no tumors of the thymus and was the only one of this group to induce tumors of the glandular stomach. Only nitrosomethylurea induced a high incidence of tumors of the nervous system, but no mammary carcinomas, which most of the other nitrosoureas induced in high incidence in females. Tumors of the lung, duodenum, colon and intestines were induced by several of the compounds, more commonly in males than in females, but a high incidence of liver tumors was found only in rats of both sexes given nitroso-2-phenylethylurea.