Hyperthermic enhancement of cisplatin-induced generation of active oxygen radicals in a cell-free system

Anticancer Res. 1998 May-Jun;18(3A):1473-7.

Abstract

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.

MeSH terms

  • Cell Line
  • Cell Survival / drug effects*
  • Cell-Free System
  • Cisplatin / pharmacology*
  • DNA, Neoplasm / drug effects
  • Female
  • Fever
  • Free Radicals / metabolism
  • Hot Temperature
  • Humans
  • Kinetics
  • Luminescent Measurements
  • Ovarian Neoplasms
  • Superoxide Dismutase / pharmacology
  • Tumor Cells, Cultured

Substances

  • DNA, Neoplasm
  • Free Radicals
  • Superoxide Dismutase
  • Cisplatin