PHOTOCYTOTOXICITY AND INTRACELLULAR GENERATION OF FREE-RADICALS BY TETRASULFONATED AL-PHTHALOCYANINES AND ZN-PHTHALOCYANINES

The photosensitizing properties of tetrasulphonated Al- and Zn-phthalo cyanines (AIPcS(4) and ZnPcS(4)) in lymphoma cells were studied as a f unction of the pre/postillumination incubation time. Photocytotoxicity increased with incubation time, ranging from a transient cell-cycle a rrest to cell killing. Under all experimental conditions, the phototox icity of ZnPcS(4) was markedly higher than that of AlPcS(4). The prima ry photoprocesses initiated by metallo-phthalocyanines (MePcS(4)) in t he cells were probed with DMPO/esr spin-trapping techniques. Under all incubation conditions the intracellularly bound MePcS(4) sensitized f ormation of three different types of DMPO spin-adducts: DMPO/OH (hydro xyl radical), DMPO/R (organic carbon-centred radical(s)) and an uniden tified simple nitroxyl, referred to as DMPO/ox. The yields of trapped radicals depended on the length of the incubation with the dyes prior to illumination and the formation of spin-adducts was shown to be intr acellular. The ability of DMPO to protect cells from the photocytotoxi c effects of Al- and ZnPcS(4), combined with the generation of carbon- centred spin-adducts is direct evidence for the involvement of free-ra dical-mediated damage of cellular constituents.