Cytotoxic effect in vivo of selected chemotherapeutic agents on synchronized murine fibrosarcoma cells

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Abstract
The cytotoxic effects in vivo of single doses of either adriamycin (ADM), 1-beta-D-arabinofuranosylcytosine (Ara-C), bleomycin (BLM), cis-diamminedichloroplatinum (II) (cis-DDP), or cyclophosphamide (CY) on murine fibrosarcoma (FSa) cell populations were determined. Tumour cells were separated and synchronized by centrifugal elutriation. Viable tumour cells from selected elutriator fractions were then injected i.v. into whole-body-irradiated mice. Twenty minutes later selected doses of ADM, Ara-C, BLM, cis-DDP or CY were administered to selected groups of these animals. Fourteen days later the mice were killed. Killing of injected tumour cells by each of the chemotherapeutic agents was evidenced by a reduction in the lung cells by each of the chemotherapeutic agents was evidenced by a reduction in the lung colonies per cell injected in treated animals. Under these conditions the response of FSa cells in vivo to the 5 drugs tested differed both qualitatively and quantitatively. Ara-C was S-phase-specific in toxicity. ADM, BLM, and cis-DDP were preferentially toxic to S, G2+M and G1 cells respectively. CY, a drug requiring bioactivation to form alkylating metabolites, was found to be equally toxic to G1 and G2+M enriched populations, but less effective in killing cell populations enriched with early-S cells.