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5-Azacytidine-modified Patterns of Uridine Kinase Activities in Normal and Neoplastic Tissues

Department of Physiological Chemistry, Ohio State University College of Medicine, Columbus, Ohio 43210 [R. C. K., T. E. W.], and Department of Biochemistry, College of Medicine, Howard University, Washington, D. C. 20001 [H. P. M.]

The murine S-37 ascites tumor and the rat Hepatoma 7800 have two forms of uridine kinase, designated I and II in order of elution from a Sepharose 6B column, which were shown earlier to correspond to the adult and embryonic forms, respectively. Although a 24-hr treatment with a single therapeutic dose of 5-azacytidine did not modify the uridine kinase profiles of these two tumors, such treatment enhanced the activity of the sole species (I) of rat liver and induced species I in Hepatoma 66 where only species II is normally present and induced species II in Hepatoma 7794A where only species I is normally present. Of particular interest is the transient 3-fold rise in species II in S-37 ascites cells during the early stages of the development of tumor resistance in response to the chronic administration of low doses of 5-azacytidine. This rise is subsequently followed by a drop in activity to below the preinduced level.

¹ Recipient of USPHS Grant CA-10729.

² Recipient of USPHS Grant CA-13718.

Received 12/10/73. Accepted 5/22/74.