Laser-induced photodynamic therapy with aluminum phthalocyanine tetrasulfonate as the photosensitizer: differential phototoxicity in normal and malignant human cells in vitro.
Photodynamic therapy (PDT) involves the use of laser or noncoherent light energy with photosensitizing dyes to induce a cytotoxic reaction in the target cells, resulting in cell injury and/or death. In this study, we have examined laser-induced phototoxicity in normal human skin fibroblasts and HT-1080 fibrosarcoma cells incubated with aluminum phthalocyanine tetrasulfonate (AlPcS) in vitro. The culture, laser, and photosensitizer parameters were varied in attempts to establish the conditions for differential cytotoxicity between normal and malignant human fibroblasts. Biochemical assays, as a measure of cytotoxicity, included [3H]thymidine incorporation (an index of DNA replication), [35S]methionine incorporation (a measure of protein synthetic activity), and the MTT assay (an indirect index of mitochondrial activity). In the absence of laser irradiation, AlPcS was non-toxic to both cell lines in concentrations up to 25 micrograms/ml. Laser light alone at 675 nm (the absorption maximum of AlPcS) had no effect on the cells at energy densities up to 16 J/cm2. In the presence of 3 or 10 micrograms/ml of AlPcS, both cell lines demonstrated marked energy-dependent toxicity. If an 8-h or a 24-h "efflux" period in AlPcS-free medium was allowed to take place prior to laser irradiation, normal fibroblasts were much less sensitive to PDT, whereas fibrosarcoma cells still exhibited a marked degree of toxicity. The results indicate that, under appropriate treatment conditions, AlPcS is capable of preferentially sensitizing a malignant mesenchymal cell line, while sparing its non-malignant normal cell counterpart.
Glassberg
E
E
Department of Dermatology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania 19107.
Lewandowski
L
L
Lask
G
G
Uitto
J
J
D005347:Fibroblasts / Q000187:drug effects / Q000528:radiation effects; D005354:Fibrosarcoma / Q000473:pathology; D006801:Humans; D007211:Indoles / Q000633:toxicity*; D007834:Lasers; D009942:Organometallic Compounds / Q000633:toxicity*; D010778:Photochemotherapy; D011838:Radiation-Sensitizing Agents / Q000633:toxicity*; D012867:Skin / Q000166:cytology; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000528:radiation effects
D007211:Indoles; D009942:Organometallic Compounds; D011838:Radiation-Sensitizing Agents; C048577:aluminum tetrasulfophthalocyanine