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Association of Decreased Uridine and Deoxycytidine Kinase with Enhanced RNA and DNA Polymerase in Mouse Leukemic Cells Resistant to 5-Azacytidine and 5-Aza-2'-deoxycytidine

J. Vesel, A. ihák and F. orm

Institute of Organic Chemistry and Biochemistry, Czechoslovak Academy of Sciences, Prague, Czechoslovakia

Resistance of mouse leukemic cells to 5-azacytidine and 5-aza-2'-deoxycytidine is associated with the partial loss of deoxycytidine kinase; at the same time, in 5-azacytidine-resistant leukemic cells uridine kinase is decreased. Furthermore, the 5-azacytidine-resistant subline exhibits increased DNA-dependent RNA and DNA polymerase activities, while its 5-aza-2'-deoxycytidine-resistant counterpart shows an enhanced RNA polymerase only. The deletion of both kinases could explain cross-resistance of 5-azacytidine-resistant leukemic cells to 5-aza-2'-deoxycytidine. 5-Aza-2'-deoxycytidine-resistant leukemic cells with unchanged uridine kinase retain their sensitivity toward 5-azacytidine. The significance of enhanced RNA and DNA polymerase activities in resistant cells is discussed.

Received 2/ 2/70. Accepted 4/16/70.