DNA ALKYLATION IN MICE WITH GENETICALLY DIFFERENT SUSCEPTIBILITY TO 1,2-DIMETHYLHYDRAZINE-INDUCED COLON CARCINOGENESIS

  • 1 January 1978
    • journal article
    • research article
    • Vol. 38  (9) , 3063-3065
Abstract
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 h. 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 40-60% less than in mice with a high incidence of colonic tumors (ICR/Ha). In hepatic DNA the extent of methylation was higher in C57BL/Ha than in lCR/Ha mice. The rate of loss of methylated purines from colon DNA was similar in both strains. In all organs investigated the metabolic incorporation of 14C into normal DNA bases was lower in C57BL/Ha than in lCR/Ha mice. The low carcinogenic response of C57BL/Ha mice is due to the smaller extent of initial alkyaltion of colon DNA, which probably reflects differences in the enzymic metabolism of the parent carcinogen.