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

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.