Inhibition of Bleomycin-Induced Toxic Effects by Antioxidants in Human Malignant Melanoma Cells

Abstract

Bleomycin is an antibiotic drug used in tumor chemotherapy. It forms a complex with iron ions which can be reduced chemically or enzymatically. The bleoraycin-Fe(II)-complex binds and activates oxygen and degrades cellular DNA. This activity of bleomycin is presumably responsible for the cytotoxic effects observed during therapy (for reviews see Burger et al., 1981; Hecht, 1986). Because reactive oxygen species are involved, we wondered whether antioxidants could inhibit bleomycin-induced cytotoxicity. For example, the seleno-organic compound Ebselen (2-pheny1–1,3-benzisoselenazo1–3(2H)one) has besides its glutathione peroxidase-like activities also antioxidant properties (Müller et al., 1984). It inhibits cell toxicity induced by adriamycin (Doroshow, 1986) and diquat (Cotgreave et al., 1987), both redox cycling compounds which can induce formation of reactive oxygen species. The other antioxidants examined were pyrogallol and propyl gallate which have also been shown to trap reactive oxygen species (Weinke et al., 1987).