1,2-Dimethylhydrazine-induced methylation of DNA bases in various rat organs and the effect of pretreatment with disulfiram.
The extent and persistence of methylated purines were determined in DNA of various rat organs following a single s.c. injection of 1,2-di[14C]methylhydrazine. Maximum alkylation of purine bases occurred within 12 hr, with highest concentrations in liver, followed by colon, ileum, and kidney. Over a period of 3 days, O6-methylguanine was removed much more slowly from colon, the principal target organ for carcinogenesis, than from ileum or liver DNA. Dietary pretreatment of rats with disulfiram is known to prevent 1,2-dimethylhydrazine-induced colon carcinogenesis and was found to reduce DNA alkylation to less than 1% of that detected in animals treated with 1,2- di[14C]methylhydrazine alone.
D000225:Adenine / Q000378:metabolism; D000818:Animals; D003106:Colon / Q000187:drug effects* / Q000378:metabolism; D004247:DNA / Q000378:metabolism*; D004127:Dimethylhydrazines / Q000378:metabolism / Q000494:pharmacology*; D004221:Disulfiram / Q000494:pharmacology*; D005260:Female; D006147:Guanine / Q000378:metabolism; D008745:Methylation; D008763:Methylhydrazines / Q000494:pharmacology*; D009928:Organ Specificity; D051381:Rats
D004127:Dimethylhydrazines; D008763:Methylhydrazines; D006147:Guanine; D004247:DNA; D000225:Adenine; D004221:Disulfiram