Effect of age on dose-response relationship in carcinogenesis induced by single administration of N-nitrosomethylurea in female rats. 1988

V N Anisimov
Laboratory of Experimental Tumors, N.N. Petrov Research Institute of Oncology, Leningrad, USSR.

Female rats aged 3 months and 15 months each received a single i.v. administration of N-nitrosomethylurea (NMU) at one of three doses: 10, 20, and 50 mg/kg. The rats exposed to NMU at the age of 3 months developed neoplasms of all sites examined, including mammary carcinomas and tumors of the kidney, ovaries and colon, the incidence varying with the carcinogen dose. The incidence of malignant neoplasms in old animals did not depend on NMU dose. In contrast to young animals, the old ones showed a higher frequency of tumors of the corpus and cervix uteri following exposure to NMU, and a lower frequency of mammary and intestinal adenocarcinomas and tumors of the ovary and kidney. Comparison of the present experimental results with the data on DNA alkylation, synthesis and O6-methylguanine repair obtained previously on the same model suggests a leading role of age-related proliferative activity changes occurring in the target tissues in the mechanism of age in modifying the effect on carcinogenesis. The analysis of data on the dose dependance of the carcinogenic effect of NMU within the framework of a multistage model suggests age-related accumulation, in different tissues, of cells occasionally lesioned and in the "late" stages of becoming malignant.

UI MeSH Term Description Entries
D008325 Mammary Neoplasms, Experimental Experimentally induced mammary neoplasms in animals to provide a model for studying human BREAST NEOPLASMS. Experimental Mammary Neoplasms,Neoplasms, Experimental Mammary,Experimental Mammary Neoplasm,Mammary Neoplasm, Experimental,Neoplasm, Experimental Mammary
D008770 Methylnitrosourea A nitrosourea compound with alkylating, carcinogenic, and mutagenic properties. Nitrosomethylurea,N-Methyl-N-nitrosourea,NSC-23909,N Methyl N nitrosourea,NSC 23909,NSC23909
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
D011919 Rats, Inbred Strains Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations or by parent x offspring matings carried out with certain restrictions. This also includes animals with a long history of closed colony breeding. August Rats,Inbred Rat Strains,Inbred Strain of Rat,Inbred Strain of Rats,Inbred Strains of Rats,Rat, Inbred Strain,August Rat,Inbred Rat Strain,Inbred Strain Rat,Inbred Strain Rats,Inbred Strains Rat,Inbred Strains Rats,Rat Inbred Strain,Rat Inbred Strains,Rat Strain, Inbred,Rat Strains, Inbred,Rat, August,Rat, Inbred Strains,Rats Inbred Strain,Rats Inbred Strains,Rats, August,Rats, Inbred Strain,Strain Rat, Inbred,Strain Rats, Inbred,Strain, Inbred Rat,Strains, Inbred Rat
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
D004260 DNA Repair The removal of DNA LESIONS and/or restoration of intact DNA strands without BASE PAIR MISMATCHES, intrastrand or interstrand crosslinks, or discontinuities in the DNA sugar-phosphate backbones. DNA Damage Response
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D005260 Female Females
D000367 Age Factors Age as a constituent element or influence contributing to the production of a result. It may be applicable to the cause or the effect of a circumstance. It is used with human or animal concepts but should be differentiated from AGING, a physiological process, and TIME FACTORS which refers only to the passage of time. Age Reporting,Age Factor,Factor, Age,Factors, Age
D000478 Alkylation The covalent bonding of an alkyl group to an organic compound. It can occur by a simple addition reaction or by substitution of another functional group. Alkylations

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