A model system for measuring comparative toxicities of cardiotoxic drugs for cultured rat heart myocytes, endothelial cells and fibroblasts. II. Doxorubicin, 5-fluorouracil and cyclophosphamide.

Separate cultures of beating myocytes (M cells), endothelial cells (E cells) and fibroblasts (F cells) from neonatal rat hearts were compared for their susceptibilities to the toxic effects of doxorubicin, 5-fluorouracil and cyclophosphamide. Toxic injury was measured as inhibition of metabolism and changes in morphology for all cell types, and changes in beating of myocytes. Cells were exposed to the anti-tumor agents for 3 days with myocytes and 7 days for endothelial cells and fibroblasts. All measures of injury were made several times the first day and daily thereafter, with the same cultures used throughout. Toxic effects of DOX and 5-FU were greater for E and F cells than for M cells, and all measures of toxicity were generally parallel. Cyclophosphamide, whether activated by liver microsomes or unactivated, was less toxic in general than the other agents, but it was more toxic for M cells than for E cells or F cells.