HYPERTHERMIC ENHANCEMENT OF CISPLATIN-INDUCED GENERATION OF ACTIVE OXYGEN RADICALS IN A CELL-FREE SYSTEM

The interaction of cisplatin [cis-diamminedichloroplatinum (II), or DD P] with calf thymus DNA has previously been shown to result in the gen eration of superoxide anions (O-2(-)) and hydroxyl radicals (OH.) in a cell-free system. The effect of hyperthermia (42 degrees C) on the ge neration of such active oxygen radicals was examined by chemiluminesce nce of a Cypridina luciferin analog (CLA) with DNA extracted from a hu man ovarian cancer cell line (A2780). Hyperthermia significantly incre ased chemiluminescence of CLA (CCLA) 1.17- to 1.51-fold at DDP concent rations of 10 to 40uM, relative to values at 37 degrees C. The extent of DDP-induced CCLA correlated significantly (r=0.973) with that of DD P cytotoxicity in A2780 cells. These results suggest that hyperthermic enhancement of DDP-induced generation of active oxygen radicals contr ibutes to the hyperthermic potentiation of DDP cytotoxicity.