In vitro evaluation of the genotoxic and clastogenic potential of photodynamic therapy.
Photodynamic therapy (PDT) was recently introduced in clinical practice for the management of cancer. As far as PDT relies on the combined action of a photosensitizer and a laser source, there is a need to evaluate the genotoxic and mutagenic potential of this treatment modality. This paper reports the effects of various photosensitizer and photo-irradiation doses on lethality to the MIA PaCa cell line using ZnPcS4 as the photosensitizer. The sister chromatid exchange (SCE) assay was used to evaluate the genotoxicity of various photosensitizer and photo-irradiation doses. Also, chromosomal aberrations at various time intervals post-irradiation were evaluated. The results showed that a combination of 3 J/cm2 irradiance with 5 microM ZnPcS4 concentration leads to the LD90 72 h post-irradiation. Eight days post-irradiation the LD90 level was achieved using a light dose of 3 J/cm2, independent of ZnPcS4 concentration. The SCE assay showed that cells treated with various light and drug doses presented no genotoxic potential, as SCE levels were not different from untreated (control) cells. Chromosomal analysis after PDT treatment at various time intervals post-irradiation showed that there was no significant chromosomal damage in cells treated photodynamically compared with untreated controls. The results show that the cell killing mechanism after PDT is not at the chromosome level, but may be at a different cellular level, such as plasma membranes, mitochondria, etc.
Halkiotis
K
K
National Technical University of Athens, Department of Electrical Engineering and Computing, Athens, Greece. halk@central.ntua.gr
Yova
D
D
Pantelias
G
G
D000230:Adenocarcinoma / Q000378:metabolism; D016923:Cell Death; D002470:Cell Survival; D002869:Chromosome Aberrations; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D066298:In Vitro Techniques; D007211:Indoles / Q000633:toxicity*; D053685:Laser Therapy; D016296:Mutagenesis; D009942:Organometallic Compounds / Q000633:toxicity*; D010179:Pancreas / Q000378:metabolism; D010778:Photochemotherapy / Q000009:adverse effects*; D017319:Photosensitizing Agents / Q000633:toxicity; D012854:Sister Chromatid Exchange; D014407:Tumor Cells, Cultured; D014410:Tumor Stem Cell Assay
D007211:Indoles; D009942:Organometallic Compounds; D017319:Photosensitizing Agents; C052735:zinc tetrasulfophthalocyanine