Photochemistry and phototoxicity studies of flutamide, a phototoxic anti-cancer drug

The phototoxic anti-cancer drug flutamide is photolabile under UV-B light i n either aerobic or anaerobic conditions. Irradiation of a methanol solutio n of this drug produces several photoproducts, one by photoreduction of the nitro group, one by rupture of the aromatic-NO2 bond of the parent compoun d, two as a result of the rupture of the GO-MI bond and one derived from th e photoreduction product by scission of the aromatic-NH2 bond. Flutamide sh ows a photohemolytic effect on human erythrocytes and photoinduces lipid pe roxidation. Studies on peripheral blood polymorphonuclear cells (neutrophil s) demonstrated the phototoxicity of flutamide as well as inhibition of the cytotoxicity respiratory burst by the photoproduct derived from its photor eduction. The results suggest that the inhibition of the respiratory burst observed in phorbol myristate acetate (PMA)-activated cells is mediated by photosensitization and concomitant singlet oxygen production and/or formati on of toxic photoproducts. (C) 2000 Elsevier Science B.V. All rights reserv ed.