DNA Alkylation in Mice with Genetically Different Susceptibility to 1,2-Dimethylhydrazine-induced Colon Carcinogenesis1
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چکیده
The formation and persistence of methylatedpurines was determinedin mice that receiveda singles.c. Injec tion of 1,2-[14Cjdimethylhydrazine (15 mg/kg) and were allowed to survive for 12 or 60 hr. In mice with a low susceptibilityto dlmethylhydrazine-lnducedcolon card nogenesis(C57BL/Ha), concentrationsof 7-methylguan inc and 06-methylguanlnein DNA of colon, ileum, and kidney were 40 to 60% less than in mice with a high incidenceof colonictumors(ICR/Ha). In hepaticDNAthe extent of methylatlonwas higher in C57BL/Ha than in ICR/Ha mice. The rate of lossof methylatedpurinesfrom colon DNA was similar in both strains. In all organs investigatedthe metabolicincorporationof 14Cinto nor mal DNA bases was lower in C57BL/Ha than in ICR/Ha mice. It Is concludedthat the low carcinogenicresponse of C57BL/Ha mice is due to the smaller extent of initial alkylatlon of colon DNA, which probably reflects differ ences in the enzymicmetabolismof the parent carcino gen.
منابع مشابه
DNA alkylation in mice with genetically different susceptibility to 1,2-dimethylhydrazine-induced colon carcinogenesis.
The formation and persistence of methylated purines was determined in mice that received a single s.c. injection of 1,2-[14C]dimethylhydrazine (15 mg/kg) and were allowed to survive for 12 or 60 hr. In mice with a low susceptibility to dimethylhydrazine-induced colon carcinogenesis (C57BL/Ha), concentrations of 7-methylguanine and O6-methylguanine in DNA of colon, ileum, and kidney were 40 to 6...
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