Comparative Metabolism of Hydrazine and Naphthalene.
Abstract
Hydrazine administration to rats and mice results in a rapid methionine-mediated methylation of nucleophilic sites in liver DNA similar to sites alkylated by chemical carcinogens. The hydrazine-provoked methylation is only weakly dose-dependent and active for less than 20 hours following a single administration of toxicant. The methylating agent in poisoned animals appears to be S-adenosylmethionine and not a methylation product of hydrazine itself (namely monomethylhydrazine). Ethionine, an antimetabolite of methionine, when given shortly before hydrazine, inhibits DNA methylation; however, if the ethionine precedes hydrazine by several hours, DNA methylation is enhanced. Treatment of rats with small doses of ethionine soon after a large dose of hydrazine results in ethylation of DNA, an observation not expected for the amount of ethionine administered. Administration of other hepatotoxins, such as carbon tetrachloride or thioacetamide, also results in methionine-mediated methylation of liver DNA in rats. Administration of doses of as little as 100 mg/kg naphthalene, a volatile hydrocarbon in shale oil, results in severe bronchiolar epithelial cell necrosis in mice. This toxicity is prevented by pretreatment with an inhibitor of cytochrome P-450 and is increased substantially by pretreatment with a depletor of reduced glutathione.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 1980
- Accession Number
- ADA092710
Entities
People
- Alan R. Buckpitt
- Louis P. Barrows
- Ronald C. Shank
Organizations
- University of California, Irvine