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Enzyme Studies in Virus-induced Neoplasms

I. The Effect of a Murine Leukemia on Enzymes of One-Carbon Metabolism and on Phosphomonoesterases^*

Robert Silber, Rody P. Cox, Jamil R. Haddad and Charlotte Friend

( Department of Medicine, New York University School of Medicine, and The Sloan-Kettering Institute, New York, New York)

The effect of infection of DBA/2 mice with the Friend leukemia virus on the activity of two groups of enzymes has been investigated. The levels of three enzymes of one-carbon metabolism, thymidylate synthetase, dihydrofolic reductase, and the formate-activating enzyme in the spleen show an increase ranging from 3 to 10 times their initial low activity during the first 2 weeks of the disease. The peak levels attained in the leukemic spleen are approximately the same as those found in subcutaneous tumors of the same cell type. Histological studies suggest that the increase in activity parallels the proliferation of neoplastic cells. The alkaline phosphatase level of the leukemic spleen decreases to about one-half of its initial activity. Similarly, alkaline phosphatase activity of subcutaneous tumors derived from leukemic organs is relatively low.

In contrast to the findings in the spleen, alkaline phosphatase of leukemic livers increases up to 15-fold from the initial level, whereas the enzymes of one-carbon metabolism in the liver are not affected. On the basis of histochemical studies and splenectomy it does not appear that the increase of hepatic alkaline phosphatase is directly related to the presence of tumor cells in the liver or to splenic enlargement.

^* This work was supported by USPHS Grants CA-06657, CA-02062, and Health Research Council Contracts U-1296, U-1096-11-C11.

Career Scientists of the Health Research Council of the City of New York.

Received 5/15/64.

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				G. H. Reem and C. Friend Phosphoribosylamidotransferase: Regulation of Activity in Virus-Induced Murine Leukemia by Purine Nucleotides Science, September 8, 1967; 157(3793): 1203 - 1204. [Abstract] [PDF]