Methylation of liver DNA guanine in hamsters given hydrazine.
Formation of 7-methylguanine and O6-methylguanine in liver DNA was measured 24 hr after administration of various single oral doses of 15 to 120 mg hydrazine/kg body wt to Syrian golden hamsters, and at various times up to 96 hr after a single oral dose of 90 mg hydrazine/kg body wt. Formation of these bases in hamster liver DNA appeared similar to that reported earlier for rats and mice treated with necrogenic doses of hydrazine; however, persistence of O6-methylguanine in liver DNA following hydrazine administration was longer in hamster than in rat liver DNA. Administration of hydrazine sulfate in the drinking water of hamsters over a 9-week period resulted in accumulation of both 7-methylguanine and O6-methylguanine in liver DNA to the extent that about 2 out of every 10,000 guanine bases were methylated at each position on the base. Diethyl maleate pretreatment of hamsters depleted liver stores of glutathione and blocked DNA methylation in hydrazine-treated animals; however, buthionine sulfoximine, which also depleted glutathione stores, had no effect on the DNA methylation response to hydrazine poisoning in Sprague-Dawley rats. Hydrazine administration to hamsters and Swiss Webster mice resulted in more 7-methylguanine and O6-methylguanine in liver DNA than did administration of monomethylhydrazine, a proposed intermediate in the hydrazine-DNA methylation response. Even at the highest feasible dose of monomethylhydrazine to hamsters, no methylguanines could be detected, while these aberrant bases were readily quantifiable following hydrazine administration; thus, no evidence was obtained to support the proposal that monomethylhydrazine is an important intermediate in the methylation of DNA guanine in hydrazine-treated animals.
D000818:Animals; D006224:Cricetinae; D004247:DNA / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005978:Glutathione / Q000032:analysis; D006147:Guanine / Q000378:metabolism*; D006834:Hydrazines / Q000633:toxicity*; D008099:Liver / Q000378:metabolism*; D008297:Male; D008647:Mesocricetus; D008745:Methylation; D009002:Monomethylhydrazine / Q000494:pharmacology; D012436:S-Adenosylmethionine / Q000378:metabolism; D013997:Time Factors
D006834:Hydrazines; D006147:Guanine; D012436:S-Adenosylmethionine; D004247:DNA; D005978:Glutathione; D009002:Monomethylhydrazine