Fred Valeriote

Cytotoxic effect of 5-fluorouracil plus cyclophosphamide against transplantable leukemias☆

The cytotoxic effect of the combination of cyclophosphamide and 5-fluorouracil against AKR and L1210 leukemias was quantitated by a spleen colony assay. We used different sequences, a number of doses of each agent, and different intervals between the agents and noted different degrees of synergistic cell-kill. By proper scheduling of these agents, greater than 100-fold increase in cell killing was noted, an effect not demonstrable for normal hematopoietic stem cells. However, the pattern of response for AKR was opposite to that for L1210 leukemia; we suggest that this reflects a difference in the metabolism of 5-FU.

Retention of 1-β-d-arabinofuranosylcytosine in vitro—: A source of experimental error

Abstract Anomalous results of dose-survival curves from studies in vitro with the nucleoside analogue 1-β- d -arabinofuranosylcytosine (ara-C) led to a consideration of distribution of drug between cells and overlying culture media. The investigations presented here, using both a biological and a radioisotope technique, demonstrate that approximately 0.5 to 1 per cent of an initial dose of ara-C is released within 1 hr into the media from treated cells and the culture dish after an initial wash.