Protection of mice against lethal doses of 1 beta-D-arabinofuranosylcytosine by pluripotent stem cell inhibitors.

The aim of this work was to study whether an inhibitor of pluripotent stem cell (CFU-S) recruitment, which we have shown previously to be able to increase the number of CFU-S after a fractionated treatment with 1-beta-D-arabinofuranosylcytosine, could increase the survival of mice given injections of lethal doses of the same drug. Two protocols of 1-beta-D-arabinofuranosylcytosine treatment were used in two different mouse strains, which both killed the mice within a week. An inhibitor of CFU-S was prepared by dialysis from fetal calf marrow, and a first step of purification was made by chromatography on Sephadex G-10. When given injections 2 hr before the drug, the number of surviving mice was increased significantly with the dialysate; fractions separated by chromatography appeared to be more effective to increase the animal survival. These preliminary results indicate that a factor of low molecular weight (below M.W. 3500) extracted from fetal calf marrow is able to protect animals during 1-beta-D-arabinofuranosylcytosine treatment. The inhibitor seems to be specific for CFU-S, without any inhibiting effect on tumor cell kinetics in vitro. If the absence of species specificity found for higher to lower species is confirmed for the lower to the higher species, then this inhibitor could be an effective tool during cancer chemotherapy.