Inhibition of DNA Methylation by S-Adenosylethionine with the Production of Methyl-deficient DNA in Regenerating Rat Liver

摘要: Ethionine, a liver carcinogen, was administered p.o. (300 mg/kg) to rats 17 hr after partial hepatectomy. At 6 administration of the ethionine, hepatic S -adenosylethionine levels were 30- 40-fold greater than level -adenosylethionine. A 10-fold ratio -adenosylmethionine still persisted at 24 ethionine adminstration. When given hepatectomy, produced 30% inhibition DNA synthesis, measured by incorporation [ methyl -3H]thymidine 23 hepatectomy (6 7 administration). synthesized during this interval deficient as judged reduced radioactivity from l-[ -3H]methionine into 5-methylcytosine residues DNA. In an assay for methylation in vitro using whole nuclei, methyl-deficient methylated 8 times more control DNA; competitively inhibited -adenosylethionine. These data suggest that -adenosylethionine, formed vivo inhibits -adenosylmethionine, resulting production DNA.