Carcinogenesis by nitrosohydroxyethylurea and nitrosomethoxyethylurea in F344 rats. 1988

W Lijinsky, and R M Kovatch
Laboratory of Chemical and Physical Carcinogenesis, NCI-Frederick Cancer Research Facility, MD 21701.

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.

UI MeSH Term Description Entries
D008297 Male Males
D009374 Neoplasms, Experimental Experimentally induced new abnormal growth of TISSUES in animals to provide models for studying human neoplasms. Experimental Neoplasms,Experimental Neoplasm,Neoplasm, Experimental
D011916 Rats, Inbred F344 An inbred strain of rat that is used for general BIOMEDICAL RESEARCH purposes. Fischer Rats,Rats, Inbred CDF,Rats, Inbred Fischer 344,Rats, F344,Rats, Inbred Fisher 344,CDF Rat, Inbred,CDF Rats, Inbred,F344 Rat,F344 Rat, Inbred,F344 Rats,F344 Rats, Inbred,Inbred CDF Rat,Inbred CDF Rats,Inbred F344 Rat,Inbred F344 Rats,Rat, F344,Rat, Inbred CDF,Rat, Inbred F344,Rats, Fischer
D002273 Carcinogens Substances that increase the risk of NEOPLASMS in humans or animals. Both genotoxic chemicals, which affect DNA directly, and nongenotoxic chemicals, which induce neoplasms by other mechanism, are included. Carcinogen,Oncogen,Oncogens,Tumor Initiator,Tumor Initiators,Tumor Promoter,Tumor Promoters,Initiator, Tumor,Initiators, Tumor,Promoter, Tumor,Promoters, Tumor
D004247 DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA, Double-Stranded,Deoxyribonucleic Acid,ds-DNA,DNA, Double Stranded,Double-Stranded DNA,ds DNA
D005038 Ethylnitrosourea A nitrosourea compound with alkylating, carcinogenic, and mutagenic properties. Nitrosoethylurea,N-Ethyl-N-nitrosourea,N Ethyl N nitrosourea
D005260 Female Females
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D012737 Sex Factors Maleness or femaleness as a constituent element or influence contributing to the production of a result. It may be applicable to the cause or effect of a circumstance. It is used with human or animal concepts but should be differentiated from SEX CHARACTERISTICS, anatomical or physiological manifestations of sex, and from SEX DISTRIBUTION, the number of males and females in given circumstances. Factor, Sex,Factors, Sex,Sex Factor
D013274 Stomach Neoplasms Tumors or cancer of the STOMACH. Cancer of Stomach,Gastric Cancer,Gastric Neoplasms,Stomach Cancer,Cancer of the Stomach,Gastric Cancer, Familial Diffuse,Neoplasms, Gastric,Neoplasms, Stomach,Cancer, Gastric,Cancer, Stomach,Cancers, Gastric,Cancers, Stomach,Gastric Cancers,Gastric Neoplasm,Neoplasm, Gastric,Neoplasm, Stomach,Stomach Cancers,Stomach Neoplasm

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