CISPLATIN GENERATES SUPEROXIDE ANION BY INTERACTION WITH DNA IN A CELL-FREE SYSTEM

Cisplatin [cis-Diamminedichloroplatinum (II), DDP] generated superoxid e anion (O-2(-)), as measured by chemiluminescence from a Cypridina lu ciferin analog (CLA), by interaction with calf thymus DNA (ct-DNA) in phosphate-buffered saline (PBS) at PH 7.6, The intensity of chemilumin escence of CLA (CCLA) increased with increased concentration of DDP, c t-DNA or CLA in the limited range of concentrations of these agents te sted. DDP-induced CCLA was completely inhibited by the addition of an O-2(-) scavenger, superoxide dismutase (SOD), or an antioxidant, ascor bic acid. Heat-inactivated SOD did not affect CCLA. The hydroxyl radic al (OH) scavengers, mannitol, ethanol, and formic acid, also caused a partial suppression of CCLA, suggesting that DDP produced OH as well a s O-2(-) in the cell-free system used. (C) 1994 Academic Press, Inc.