Amiloride but not bumetanide protects against the cytotoxic effects of estramustine and bleomycin in cultured fibroblasts.

The effects of the clinically used diuretics amiloride (an inhibitor of Na+/H+ exchange) and bumetanide (an inhibitor of Na+, K+, Cl- co-transport) were tested on the cytotoxicity of estramustine and bleomycin in cultured fibroblasts. Both estramustine (50 micrograms/ml) and bleomycin (10 micrograms/ml) reduced the number of surviving clones. Amiloride (100 microM) but not bumetanide (100 microM) partly protected against the cytotoxic effect of both estramustine and bleomycin. The protective effect of the combination of amiloride and bumetanide was not stronger than the effect of amiloride alone. Amiloride or bumetanide alone did not affect the clonal survival. It is suggested that the protective effect of amiloride is not mediated by an effect of the molecular mechanism of cytotoxicity but may rather be due to changes in cellular metabolism and/or drug handling.