Hyperthermic enhancement of cisplatin-induced generation of active oxygen radicals in a cell-free system.
The interaction of cisplatin [cis-diamminedichloroplatinum (II), or DDP] with calf thymus DNA has previously been shown to result in the generation of superoxide anions (O2-) and hydroxyl radicals (OH) in a cell-free system. The effect of hyperthermia (42 degrees C) on the generation of such active oxygen radicals was examined by chemiluminescence of a Cypridina luciferin analog (CLA) with DNA extracted from a human ovarian cancer cell line (A2780). Hyperthermia significantly increased chemiluminescence of CLA (CCLA) 1.17- to 1.51-fold at DDP concentrations of 10 to 40 uM, relative to values at 37 degrees C. The extent of DDP-induced CCLA correlated significantly (r = 0.973) with that of DDP cytotoxicity in A2780 cells. These results suggest that hyperthermic enhancement of DDP-induced generation of active oxygen radicals contributes to the hyperthermic potentiation of DDP cytotoxicity.
Department of Surgery, Kyushu Dental College, Kitakyushu, Japan.
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Masuda
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Tanaka
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Matsushima
D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects*; D002474:Cell-Free System; D002945:Cisplatin / Q000494:pharmacology*; D004273:DNA, Neoplasm / Q000187:drug effects; D005260:Female; D005334:Fever; D005609:Free Radicals / Q000378:metabolism; D006358:Hot Temperature; D006801:Humans; D007700:Kinetics; D008163:Luminescent Measurements; D010051:Ovarian Neoplasms; D013482:Superoxide Dismutase / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D004273:DNA, Neoplasm; D005609:Free Radicals; D013482:Superoxide Dismutase; D002945:Cisplatin