Abstract
Liver DNA of young adult male Fischer 344 rats given orally a necrogenic dose of hydrazine (60 mg/kg body wt) rapidly became methylated at the 7-position of guanine, and more slowly and to a lesser extent at the O 6-position of guanine. The identity of 7-methylguanine from liver DNA of hydrazine-treated rats was confirmed by four high-pressure liquid chromatographic methods, in one paper chromatography system, and by ultraviolet absorption spectrometry. Similar evidence was obtained to support the identification of O 6-methylguanine. Liver DNA isolated from rats given hydrazine and [ methyl- 3H]methionine contained 7-methylguanine and O 6-methylguanine which were labeled to a greater extent than was the parent base, guanine, suggesting that S-adenosylmethionine was the methyl source in the alkylation of DNA. Aberrant methylation of liver DNA was also observed in rats after administration of hepatotoxic doses of carbon tetrachloride and ethanol, indicating that the DNA methylation may be a nonspecific response to chemical injury to the liver.
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