Effect of pH and elevated temperatures on the cytotoxicity of some chemotherapeutic agents on Chinese hamster cells in vitro.

The cytotoxicity of some drugs is a function of extracellular pH. We show that this dependence is greatly enhanced at 43 degrees. At this temperature, we have examined the cell-killing ability of four drugs in the pH range of 6.5 to 8.5. For 1,3-bis(2-chloroethyl)-1-nitrosourea, cytotoxicity is minimum at alkaline pH and increases in monotonic fashion as the milieu becomes more acidic. There is little or no effect of pH on the cytotoxicity of methotrexate. Bleomycin is most effective at acidic pH (less than 7.5). Above that pH, its cytotoxicity remains unchanged. Amphotericin B is least cytotoxic at the pH of normal tissue, 7.4. At higher or lower values, its cell-killing efficiency increases symmetrically. These results may have some relevance in designing thermo-chemotherapeutic treatment protocols.