1-β-d-Arabinofuranosylcytosine (ara-C3 or cytosine arabinoside), a pyrimidine nucleoside analog, is capable of inhibiting marrow regeneration in lethally irradiated mice in which marrow recolonization by donor marrow cells from normal mice occurs. When administered on the 4th day after irradiation and marrow injection, the drug induces significant marrow suppression. Depending upon the relative amounts of the compounds and the intervals of time between their administration, reversal of the effect of cytosine arabinoside on the bone marrow can be accomplished by deoxycytidine. When the metabolic block induced by cytosine arabinoside is circumvented by deoxycytidine, with release of the biosynthesis of DNA, the administration of certain cytotoxic agents yields enhanced suppression of the regenerating bone marrow of mice.
Supported by USPHS Grants CA-02817, CA-05944, CA-5138, and MO-FR38.
The abbreviations used are: ara-C, cytosine arabinoside (1-β-d-arabinofuranosylcytosine hydrochloride); DNA, deoxyribonucleic acid; CdR, 2′-deoxycytidine; IUdR, 5-iodo-2′-deoxyuridine; HN2, nitrogen mustard.