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Enzymes of Thymidine Triphosphate Synthesis in Selected Morris Hepatomas^{1 ,2}

McArdle Memorial Laboratory, The Medical School, University of Wisconsin, Madison, Wisconsin 53706

The activities of certain enzymes catalyzing reactions leading to the synthesis of thymidine triphosphate were analyzed in vitro in minimal deviation type Morris hepatomas of normal karyotype as well as in Novikoff and Reuber H-35 cells from tissue culture and in Ehrlich ascites cells. Most Morris hepatomas had normal or near-normal levels of deoxycytidine monophosphate deaminase, while Novikoff and Ehrlich cells and rat thymus and bone marrow showed extreme elevations in activity of this enzyme. The Novikoff, H-35, and Ehrlich ascites cells, and all of the Morris hepatomas except 9633, had elevated deoxythymidine monophosphate (dTMP) synthetase activity. All of the hepatomas and tissue culture material exhibited elevations in deoxythymidine (TdR) kinase and possibly dTMP kinase activities. Hepatomas 5123C, 7800, and 9618A possessed the ability to degrade thymine at lesser rates than normal adult rat liver, while hepatoma 9633 and Novikoff and H-35 cells from tissue culture apparently lacked thymine degradative ability. With the exception of dTMP synthetase, the activities of these enzymes in normal karyotype Morris hepatomas showed no quantitative relationship with growth rate. Among the hepatomas and enzymes reported, TdR kinase was the only enzyme with consistently elevated activity. These results and certain unpublished data are discussed with respect to possible alternative routes to deoxythymidine triphosphate synthesis and the chemotherapy of cancer.

¹ This work was supported in part by Grant No. P-448 from the American Cancer Society, by USPHS Grant No. TO1-CA-5002 from the National Cancer Institute, and by USPHS Grant No. CA-10729. A preliminary report was given before the American Association for Cancer Research in Chicago, Illinois, in April 1967 (50).

² This paper is the fifth in a series entitled The Comparative Enzymology and Cell Origin of Rat Hepatomas.

³ Laboratory of Biochemistry, National Cancer Institute, NIH, Bethesda, Maryland 20014. Present address: Department of Biochemistry, College of Medicine, Howard University, Washington, D. C. 20001. Supported in part by USPHS Grant No. CA-10729.

Received 2/23/68. Accepted 9/ 5/68.