DNA methylation during chronic administration of 1,2-dimethylhydrazine in a carcinogenic regimen.
The formation and persistence of O6-methylguanine and 7-methylguanine in colon, kidney, and liver DNA were measured over a period of 25 weeks 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 one week 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 was seen to accumulate in liver DNA. The concentrations of O6-methylguanine and 7-methylguanine in kidney DNA did increase with reported administration of the carcinogen, but these bases were removed within six weeks after the last (14th) injection of SDMH. Large amounts of 7-methylguanine accumulated in liver DNA over the 14-week 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 increase at a rate greater than would be expected from calculations based on the rate of removal following a single administration of SDMH.
D019813:1,2-Dimethylhydrazine; D000818:Animals; D002273:Carcinogens; D003106:Colon / Q000378:metabolism; D004247:DNA / Q000378:metabolism*; D004127:Dimethylhydrazines / Q000633:toxicity*; D005260:Female; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D008745:Methylation; D008763:Methylhydrazines / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains
D002273:Carcinogens; D004127:Dimethylhydrazines; D008763:Methylhydrazines; D004247:DNA; D019813:1,2-Dimethylhydrazine