Effect of pretreatment of rats with N-methyl-N-nitrosourea on the repair of O(6)-methylguanine in liver DNA. 1981

G P Margison

The capacity of rat liver to repair O6-methylguanine was determined by measuring the amounts of this base present in DNA after administration of N-[14C]methyl-N-nitrosourea (MNU). Chronic pretreatment of animals with unlabelled MNU either once weekly for 5 weeks or daily on weekdays for 14 days had either no marked effect or inhibited (or overloaded) repair activity, respectively. Pretreatment of rats with single doses of MNU initially decreased O6-methylguanine repair but this effect was lost as the pretreatment interval increased and by 40 h, activity had returned to control values. Administration of methylmethanesulphonate for 14 days had no effect on the removal of O6-methylguanine produced in liver DNA by [14C]MNU. None of the pretreatment schedules inhibited the removal of 3-methyladenine from liver DNA. These effects are contrasted with those produced by pretreatment of rats with dimethylnitrosamine (DMN) or 1,2-dimethylhydrazine which enhanced the capacity of the liver to remove O6-methylguanine produced by single dose of [14C]DMN.

UI MeSH Term Description Entries
D008297 Male Males
D008745 Methylation Addition of methyl groups. In histo-chemistry methylation is used to esterify carboxyl groups and remove sulfate groups by treating tissue sections with hot methanol in the presence of hydrochloric acid. (From Stedman, 25th ed) Methylations
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
D009607 Nitrosourea Compounds A class of compounds in which the core molecule is R-NO, where R is UREA. Compounds, Nitrosourea
D004127 Dimethylhydrazines Hydrazines substituted with two methyl groups in any position. Dimethylhydrazine
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
D006147 Guanine
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
D051381 Rats The common name for the genus Rattus. Rattus,Rats, Laboratory,Rats, Norway,Rattus norvegicus,Laboratory Rat,Laboratory Rats,Norway Rat,Norway Rats,Rat,Rat, Laboratory,Rat, Norway,norvegicus, Rattus
D019813 1,2-Dimethylhydrazine A DNA alkylating agent that has been shown to be a potent carcinogen and is widely used to induce colon tumors in experimental animals. 1,2-Dimethyl-hydrazine,N,N'-Dimethylhydrazine,SDMH,sym-Dimethylhydrazine,1,2 Dimethyl hydrazine,1,2 Dimethylhydrazine,N,N' Dimethylhydrazine,sym Dimethylhydrazine

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