Hyperthermic potentiation of cis-diamminedichloroplatinum(II) cytotoxicity in Chinese hamster ovary cells resistant to the drug.
The cytotoxic and pharmacological properties of hyperthermia and cis-diamminedichloroplatinum(II) (DDP) were studied in DDP-sensitive and DDP-resistant Chinese hamster ovary cells in vitro. Cytotoxicity was measured by cell survival using colony formation assay and cellular platinum levels were determined by atomic absorption spectrophotometry. Hyperthermia potentiated DDP cytotoxicity in both DDP-sensitive and DDP-resistant Chinese hamster ovary cells. Dose enhancement ratios increased from 1.4 to 6.5 over the temperature range of 39-43 degrees C. Cellular accumulation of platinum at 37 degrees C in the sensitive cells was 2.3- to 3.3-fold greater than that in the drug-resistant cells. Cellular accumulation of DDP was increased by factors of 1.5 and 2.2 at elevated temperature. DDP resistance did not confer cross-resistance to heat alone. The results suggest that hyperthermia could be used to circumvent DDP resistance.
D000818:Animals; D002330:Carmustine / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002945:Cisplatin / Q000494:pharmacology*; D006224:Cricetinae; D003412:Cricetulus; D004351:Drug Resistance; D006358:Hot Temperature
D002945:Cisplatin; D002330:Carmustine