Carcinogenesis by Nitrosohydroxyethylurea and Nitrosomethoxyethylurea in F344 Rats

Nitroso ‐ 2 ‐ hydroxyethylurea and its methyl ether, nitroso ‐ 2 ‐ methoxyethylurea, were administered to male and female rats by gavage, each at two dose rates. The highest dose rate of nitrosohydroxyethylurea was 14 mg twice a week for 18 weeks, which led to death of all animals by week 34 with a variety of neoplasms, which have been observed in earlier experiments at lower doses, and included those in lung, colon, thyroid, forestomach, tongue, duodenum, jejunum, Zymbal's gland, thymus and mammary gland adenocarcinomas. At a dose 10 times smaller, the animals survived much longer, but the distribution of tumors was similar, except that there were few of the duodenum and jejunum. At an equimolar dose of nitrosomethoxyethylurea (1.6 mg, twice a week), the pattern of tumors was similar to that seen with nitrosohydroxyethylurea, including the absence of tumors in the duodenum and jejunum, although there were tumors of the colon. The rats treated with the methyl ether died earlier than those given nitrosohydroxyethylurea, indicating a greater potency of the former. At a dose of 3.2 mg twice a week, nitrosomethoxyethylurea produced the same pattern of tumors as the lower dose, but the animals died earlier. In all groups, there were more lung tumors in males than in females, and this was true to a lesser extent of the colon. The main effect of methylation of the hydroxyl group in nitrosohydroxyethylurea was to increase the potency of the carcinogen, but there was no effect on the target organ specificity of the nitrosourea.