Enhanced formation of reactive species from cis-diammine-(1,1-cyclobutanedicarboxylato)- platinum(ii) (carboplatin) in the presence of oxygen free radicals

摘要: Abstract Experiments were designed to investigate the influence of oxygen free radicals on rate conversion anticancer drug cis -diammine-(1,1-cyclobutanedicarboxylato)platinum(II) (CBDCA) reactive species able bind DNA. A system containing Fe-EDTA chelate and ascorbate was used generate radicals. The by-products, during incubation in chloride-free phosphate buffer at 37°, determined by HPLC analysis found be approximately 10 times faster presence radical generating system, compared CBDCA alone. hydroxyl scavenger, mannitol, reduce significantly, while an enhancing effect observed Superoxide dismutase. platinum species, which are formed radicals, demonstrated react with isolated salmon sperm binding DNA Fe-EDTA/ascorbate markedly enhanced. No -diamminedichloroplatinum(II) (CDDP) same experimental conditions observed, thus excluding increased susceptibility itself platinum, due damage induced These findings support hypothesis that CBDCA, previously our laboratory, occurs hemoglobin could mediated a Fenton-like reaction resulting production, providing potential clues improvements clinical use this drug.