Evaluation of hypoxia and acidosis on the cytotoxicity of the stereoisomers of tetraplatin at normal and hyperthermic temperatures.
Tetraplatin is a second-generation platinum analogue that will be introduced into clinical trials during 1990. We have evaluated the cytotoxicity of tetraplatin and its stereoisomers under a variety of conditions in a human solid tumour cell line (A549). The d-trans stereoisomer of tetraplatin is the most cyutotoxic form of the drug under all conditions examined. Simultaneous treatment with hyperthermia (43 degrees C) resulted in a greater than 1 log increase in cytotoxicity over tetraplatin (10 micrograms/ml) alone. Lowering the pH of the media from 7.4 to 6.4 did not significantly modify the cytotoxicity of tetraplatin at 37 degrees C or at 43 degrees C. Under acidic pH (6.4) hypoxia did not alter the cytotoxicity of tetraplatin at 37 degrees C or 43 degrees C. These results indicate a potential therapeutic advantage of combining tetraplatin chemotherapy with hyperthermia, which appears to be uneffected by acidic and/or hypoxic conditions.
Department of Surgery, University of Wisconsin, Madison 53792.
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D000138:Acidosis / Q000378:metabolism; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D015687:Cell Hypoxia / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D006358:Hot Temperature / Q000627:therapeutic use*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D009944:Organoplatinum Compounds / Q000737:chemistry / Q000494:pharmacology*; D013237:Stereoisomerism; D014407:Tumor Cells, Cultured / Q000187:drug effects* / Q000378:metabolism
D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; C049777:ormaplatin