This Article Full Text (PDF) Erratum (v31,p482) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Labow, R. Articles by Maley, F. Search for Related Content PubMed PubMed Citation Articles by Labow, R. Articles by Maley, F.

The Effect of Methotrexate on Enzymes Induced following Partial Hepatectomy¹

Division of Laboratories and Research, New York State Department of Health, Albany, New York 12201

The synthesis of thymidine kinase, thymidylate kinase, thymidylate synthetase, DNA polymerase, and deoxycytidylate deaminase was initiated at about 12 hr following partial hepatectomy of rats. The intraperitoneal injection of Methotrexate inhibited the synthesis of all of the above enzymes with the exception of thymidylate synthetase, which was markedly stimulated. The synthetase activity was fourfold greater than that of the uninjected controls at 48 hr following partial hepatectomy, and at 72 hr it was 10- to 15-fold higher. At the latter time interval, the synthetase was still increasing in activity in the treated rats, while the enzyme activity in the control rat livers was decreasing. Puromycin had no effect on the synthetase elevation, while actinomycin inhibited the increase partially. However, cycloheximide, at levels that did not inhibit the normal rise in deoxycytidylate deaminase activity following partial hepatectomy, greatly inhibited the normal and Methotrexate-stimulated increase in synthetase activity. To emphasize the possibility that the Methotrexate stimulation may be an indirect effect, folate was found to cause a similar, though less dramatic, increase in thymidylate synthetase activity.

¹ This work was supported in part by USPHS Research Grant CA-06406 from the National Cancer Institute.

² Public Health Service Research Career Development Awardee (5-K3-CA-28, 119-02) of the National Cancer Institute.

Received 6/ 7/68. Accepted 10/23/68.