DNA methylation during chronic administration of 1,2-dimethyl-hydrazine in a carcinogenic regimen

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Abstract
The formation and persistence of O6-methylguanine and 7-methylguanine in colon, kidney and liver DNA were measured over a period of 25 wk during 1,2-dimethylhydrazine (SDMH) carcinogenesis. Rats were given 14 weekly s.c. injections of 21 mg SDMH/kg body wt., and methylated guanines in DNA were determined quantitatively 1 wk after each injection to measure the long-term accumulation of these aberrant bases. No accumulation of either base was seen in colon DNA, and no O6-methylguanine accumulated in liver DNA. The concentrations of O6-methylguanine and 7-methylguanine in kidney DNA did increase with repeated administration of the carcinogen, but these bases were removed within 6 wk after the last (14th) injection of SDMH. Large amounts of 7-methylguanine accumulated in liver DNA over the 14-wk treatment period. The concentration of 7-methylguanine in liver and kidney DNA increased at rates greater than could be accounted for by using kinetic relationships determined in single-exposure studies. The concentration of O6-methylguanine in kidney DNA also increased at a rate greater than would be expected from calculations based on the rate of removal following a single administration of SDMH.