Photocytotoxicity and intracellular generation of free radicals by tetrasulphonated Al- and Zn-phthalocyanines.
The photosensitizing properties of tetrasulphonated Al- and Zn-phthalocyanines (AlPcS4 and ZnPcS4) in lymphoma cells were studied as a function of the pre/post-illumination incubation time. Photocytotoxicity increased with incubation time, ranging from a transient cell-cycle arrest to cell killing. Under all experimental conditions, the phototoxicity of ZnPcS4 was markedly higher than that of AlPcS4. The primary photoprocesses initiated by metallo-phthalocyanines (MePcS4) in the cells were probed with DMPO/esr spin-trapping techniques. Under all incubation conditions the intracellularly bound MePcS4 sensitized formation of three different types of DMPO spin-adducts: DMPO/OH (hydroxyl radical), DMPO/R (organic carbon-centred radical(s)) and an unidentified 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 intracellular. The ability of DMPO to protect cells from the photocytotoxic effects of Al- and ZnPcS4, combined with the generation of carbon-centred spin-adducts is direct evidence for the involvement of free-radical-mediated damage of cellular constituents.
Gantchev
T G
TG
Department of Nuclear Medicine and Radiobiology, Faculty of Medicine, University of Sherbrooke, Quebec, Canada.
Urumov
I J
IJ
Hunting
D J
DJ
Van Lier
J E
JE
D002478:Cells, Cultured; D003497:Cyclic N-Oxides; D005609:Free Radicals; D006801:Humans; D007211:Indoles / Q000378:metabolism / Q000494:pharmacology*; D008027:Light; D009942:Organometallic Compounds / Q000378:metabolism / Q000494:pharmacology*; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*
D003497:Cyclic N-Oxides; D005609:Free Radicals; D007211:Indoles; D009942:Organometallic Compounds; D011838:Radiation-Sensitizing Agents; C048577:aluminum tetrasulfophthalocyanine; C052735:zinc tetrasulfophthalocyanine; C017245:5,5-dimethyl-1-pyrroline-1-oxide