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Department of Radiology, Stanford University School of Medicine, Stanford, California 94305
The cytotoxicity of some drugs is a function of extracellular pH. We show that this dependence is greatly enhanced at 43°. 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 (<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 thermochemotherapeutic treatment protocols.
1 Supported by Grants CA 04542 and CA 19386 from the National Cancer Institute.
2 To whom requests for reprints should be addressed.
Received 6/ 3/83. Accepted 9/ 2/83.
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