Lethal photosensitization by endogenous porphyrins of PAM cells--modification by desferrioxamine.
The effects of exogenous delta-aminolevulinic acid (ALA) on cultured PAM 212 cells were investigated. PAM cells exposed to ALA produce an excess of products of the heme biosynthesis pathway within hours. The endogenous porphyrins render the cells photosensitive in a time-, ALA dose- and irradiation-dependent manner. Independently of the ALA-induced photosensitized processes, ALA itself reduces the proliferation rate of PAM cells during the exponential growth phase. Iron deprivation by addition of the chelating agent desferrioxamine (df) accelerates the photosensitizing process, and thus makes it more efficient at lower ALA concentrations. The effects of df were compared with the effects of manganese-df and iron-df. The results indicate that iron trapping is the most important factor for the potentiation of ALA-stimulated photodynamic sensitization as well as for the dark toxicity. Iron complexing agents may thus be used to optimize ALA effects in the photodynamic treatment of cutaneous neoplasms with endogenous porphyrins.
Ortel
B
B
Division of Special and Environmental Dermatology I, University of Vienna, School of Medicine, Austria.
Tanew
A
A
Hönigsmann
H
H
D000622:Aminolevulinic Acid / Q000494:pharmacology*; D000818:Animals; D002294:Carcinoma, Squamous Cell; D002455:Cell Division / Q000187:drug effects / Q000528:radiation effects; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D004261:DNA Replication; D003624:Darkness; D003676:Deferoxamine / Q000494:pharmacology*; D008027:Light; D051379:Mice; D011166:Porphyrins / Q000502:physiology*; D013936:Thymidine / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014410:Tumor Stem Cell Assay
D011166:Porphyrins; D000622:Aminolevulinic Acid; D003676:Deferoxamine; D013936:Thymidine