The early changes in the metabolism of L-ethionine were examined in rats preexposed to chronic administration of DL-ethionine. The capacity of liver to accumulate S-adenosylethionine after a single injection of L-ethionine decreases rapidly from the onset of the carcinogenic regimen. This drop is caused by diminished S-adenosylethionine synthesis, a consequence of lower activity of the ATP-L-methionine adenosyltransferase. This change is accompanied by the rapid increase of the concentration of

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... free ethionine and ethionine sulfoxide. The concentration of hepatic ATP depends in the control animals on the L-ethionine dose and is inversely related to the S-adenosylethionine concentration, but in DL-ethionine-pretreated rats it becomes gradually independent of the L-ethionine dose. The alterations in L-ethionine metabolism observed are not attributed to the change in the ratio of hepatocytes to oval cells but rather to the functional alterations of hepatocytes.