Effect of cell growth and cell differentiation on 1‐β‐d‐arabinofuranosylcytosine metabolism in myeloid cells

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Abstract
Summary. Resistance of leukaemic blasts to 1‐β‐D‐arabinofuranosylcytosine (ara‐C) has been shown to be associated with changes in the metabolism of this drug. However, effects of cell growth and maturation stage on ara‐C metabolizing enzymes have to be excluded as a possible cause of different enzyme activities in leukaemic blasts between nonresponders and patients achieving complete remission. We evaluated the effects of cell cycle phase and cell differentiation on the activity of cytidine deaminase, deoxycytidylate deaminase and deoxycytidine kinase in myeloid cell lines. Our data indicate that different enzyme profiles in nonresponders might not only be caused by the emergence of mutator phenotypes but may also reflect the growth and maturation stage of leukaemic blasts.