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Formation of S-Adenosylethionine in Liver of Rats Chronically Fed with DL-Ethionine¹

Papanicolaou Comprehensive Cancer Center, University of Miami School of Medicine, Miami, Florida 33101

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 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.

¹ Supported by USPHS Grant 1 RO1 CA 23516 awarded by the National Cancer Institute. This work was presented in preliminary from at the FASEB meeting (1).

² To whom requests for reprints should be addressed, at P.O. Box 016188, Miami, FL 33101.

³ This paper is a part of a doctoral thesis at the Julius-Maximilians University, Wuerzburg, Federal Republic of Germany. Supported by "Deutscher Akademischer Austauschdienst."

⁴ Deceased April 27, 1985.

Received 11/11/86. Revised 9/25/87. Revised 2/23/88. Revised 5/ 4/88. Accepted 5/13/88.

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