Protective effect of iron chelators on epirubicin-induced fibroblast toxicity

Free oxygen radicals generated by anthracycline/iron complexes have been implicated in anthracycline cytotoxicity. We therefore tested whether enzymatic scavengers of free radicals or metal chelators were able to inhibit anthracycline toxicity. The survival of Chinese hamster fibroblasts was reduced when the cells were exposed to 0.1-1.0 mg/l 4'-epidoxorubicin (epirubicin). Superoxide dismutase (SOD) (250 mg/l), or catalase (250 mg/l) did not affect the clonogenic survival of the fibroblasts. The metal-chelators, diethylenetriamine-pentaacetic acid (DTPA) (100 mumol/l), EDTA (100 mumol/l), and desferrioxamine (100 mumol/l) all protected against epirubicin-induced clonogenic survival. The protection of chelators against epirubicin toxicity implies that chelators might also be able to modulate anthracycline toxicity in vivo.