INVIVO KINETICS OF O6-METHYLGUANINE AND 7-METHYLGUANINE FORMATION AND PERSISTENCE IN DNA OF RATS TREATED WITH SYMMETRICAL DIMETHYLHYDRAZINE

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  • 1 January 1981
    • journal article
    • research article
    • Vol. 41  (10) , 3967-3972
Abstract
The rates of appearance and removal of 7-methylguanine and O6-methylguanine in DNA from rat liver, kidney and colon were determined at various intervals up to 120 h after i.p. administration of 10.2, 40.7, 81.5, or 163 mg 1,2-dimethylhydrazine (SDMH)/kg body wt (1/16, 1/4, 1/2, or 1 50% lethal dose) using high-pressure liquid chromatography and fluorescence spectrophotometry. In most cases increasing doses of SDMH slowed the rate of methylation of DNA, especially of the liver; colon DNA was methylated at a faster rate than was liver DNA; and kidney DNA was methylated at the slowest rate. Removal of O6-methylguanine was slow (half-life [t1/2], 37-50 h) when this base was present in liver DNA at concentrations > 400 .mu.mol/mol guanine; as the concentration fell to < 300 .mu.mol O6-methylguanine/mol guanine, the removal rate more than doubled (t1/2 16-19 h). In the first 12 h after maximum DNA methylation following SDMH administration, a rapid time-dependent removal of 7-methylguanine from liver and kidney but not colon DNA evidently occurred. In these instances, the rates of formation and removal of aberrant methylated bases did not follow 1st-order kinetics.