Cytotoxic effect of adriamycin in vivo on synchronized murine fibrosarcoma cellst

Abstract

The cytotoxic effect of Adriamycin (ADR) on synchronized fibrosarcoma (FSa) cells lodged in the lungs of specific pathogen free C 3Hf/Bu mice was determined. FSa cells from primary asynchronous cultures were separated and synchronized on the basis of cell size by centrifugal elutriation. Cell cycle parameters were determined by flow micro-fluorometry (FMF). Viable tumor cells from each elutriator fraction were injected intravenously into recipient mice. Twenty minutes later, ADR (10 mg/kg) was administered intravenously into half of the animals in each group. After fourteen days the animals were killed, and the resulting lung colonies were counted. Under these conditions, the S-phase enriched populations were found to be the most sensitive to ADR. Cell survival ranged from a maximum of 8% to a minimum of 0.3% for the Gi and S-phase enriched populations, respectively. Dose response curves were also determined for selected populations treated in vivo. While no great difference in Do was observed between the survival curves representing each of these populations (range, 0.65–0.71 mg/kg), the extrapolation numbers varied from 0.41 (51% S-phase) to 2.1 (9% S-phase).