IMINIUM SALT OF COPPER BENZOCHLORIN (CDS1), A NOVEL PHOTOSENSITIZER FOR PHOTODYNAMIC THERAPY - MECHANISM OF CELL-KILLING

The mechanism of cell killing by CDS1, an iminium salt of octaethylben zochlorin with copper in the aromatic ring, in combination with light from a noncoherent light source was investigated. Using a standard clo nogenic assay and the AY-27 FANFT tumor line, photoactivation of CDS1 was shown to be cytotoxic. The photodynamic cell killing ability of CD S1 required the presence of molecular oxygen. The reactive species gen erated by light activation of CDS1 were effectively quenched by N,N'-d iphenyl-p-phenylenediamine. Additionally, the photodynamic effect of C DS1 was not enhanced by deuterium oxide. To characterize the reactive oxygen species generated by the photoactivation of CDS1 the well-chara cterized erythrocyte ghost model was used. Superoxide dismutase and ca talase were potent inhibitors of CDS1-induced lipid peroxidation of er ythrocyte membranes. Sodium azide only partially inhibited lipid perox idation. These findings differed from the known singlet oxygen generat or, tin (II) etiopurpurin dichloride (SnET2). Sodium azide was a poten t inhibitor of SnET2-induced lipid peroxidation, whereas superoxide di smutase and catalase were totally ineffective. Based on these results, we conclude that CDS1 requires the presence of molecular oxygen for c ell killing to occur but appears to act primarily through a non-single t oxygen mechanism.