1. Modulation of the cytotoxicity of porfiromycin by dicoumarol in vitro and in vivo.
- Author
-
Rockwell S, Keyes SR, and Sartorelli AC
- Subjects
- Animals, Cell Line, Cell Survival drug effects, Mice, Mice, Inbred BALB C, Porfiromycin pharmacology, Porfiromycin therapeutic use, Tumor Cells, Cultured cytology, Tumor Cells, Cultured drug effects, Tumor Stem Cell Assay, Dicumarol therapeutic use, Mammary Neoplasms, Experimental drug therapy, Mitomycins toxicity, Porfiromycin toxicity
- Abstract
The effects of dicoumarol (DIC) on the cytotoxicity of porfiromycin (POR) were studied in vitro using EMT6 mammary tumor cells in monolayer cultures and in vivo using solid EMT6 tumors and bone marrow stem cells. In vitro, POR was more toxic to hypoxic EMT6 cells than to aerobic cells. Exposure of aerobic cultures to DIC protected against POR; in contrast, DIC sensitized hypoxic cells to POR. Treatment of mice with DIC produced a slight increase in the toxicity of POR to cells in solid tumors. The toxicity of POR to marrow stem cells (CFU-GM and CFU-MK) was not altered by DIC. Pretreatment of mice with DIC therefore produced a small improvement in the therapeutic ratio.
- Published
- 1989