The relation of exposure time and drug concentration in their effect on cloning efficiency after incubation of human bone marrow with cytosine arabinoside

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Abstract
Summary. The effect of different cytosine arabinoside (Ara‐C) concentrations and exposure times upon clonogenicity of normal bone marrow cells was studied. One hour incubation, even at the pharmacologically high Ara‐C concentration of 10−5 M, was not cytotoxic. Prolonged incubation resulted in a very great increase in Ara‐C cytotoxicity, provided that inactivation of Ara‐C by deamination was limited. The results show that long‐term exposure to Ara‐C, even at pharmacologically very low concentrations, is deleterious to clonogenic cells and provide an experimental basis for the reported therapeutic efficacy of long‐term low dose Ara‐C administration in leukaemia and preleukaemic syndromes.