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.