Evidence for indirect genetic damage as methylation of DNA guanine in response to cytotoxicity.
Administration of hepatotoxic doses of the inorganic carcinogen, hydrazine, to rodents results in the rapid formation of methylguanines in liver DNA, the methyl donor presumably being S-adenosylmethionine. The DNA methylation pattern after hydrazine administration is qualitatively similar to that seen after dimethylnitrosamine administration, and this type of genotoxicity is thought to be part of the initiation process in chemical carcinogenesis. Preliminary evidence suggests that the methylation of liver DNA guanine may be an endogenous response to the cytotoxicity caused by hydrazine rather than due to any intrinsic property of the chemical itself. These investigations represent an approach to the study of the causal role, if any, of toxicity in chemical carcinogenesis.
D000818:Animals; D002273:Carcinogens; D004247:DNA / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006147:Guanine / Q000031:analogs & derivatives / Q000378:metabolism*; D006168:Guinea Pigs; D006834:Hydrazines / Q000633:toxicity; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008745:Methylation; D051379:Mice; D051381:Rats; D011919:Rats, Inbred Strains
D002273:Carcinogens; D006834:Hydrazines; D006147:Guanine; C008450:7-methylguanine; D004247:DNA; C008449:O-(6)-methylguanine