Mutagenicity of photodynamic therapy as compared to UVC and ionizing radiation in human and murine lymphoblast cell lines.
The mutagenicity of photodynamic therapy (PDT) using red light and either Photofrin (porfimer sodium) (PF) or aluminum phthalocyanine (AlPc) as the photosensitizer was determined at the thymidine kinase (TK) locus in the human lymphoblastic cell lines, TK6 and WTK1, and was compared to the mutagenicity of UVC and X-radiation in these cells as well as the mutagenicity of PDT in murine L5178Y lymphoblastic cell lines. Photodynamic therapy was found not to be mutagenic in TK6 cells, which possess an active p53 gene and which are relatively deficient in recombination and repair of DNA double-strand breaks. In contrast, PDT with either sensitizer was significantly mutagenic in WTK1 cells, which harbor an inactivating mutation in the p53 gene and are relatively efficient in recombination and double-strand break repair as compared to TK6 cells. The induced mutant frequency in WTK1 cells with PF as the photosensitizer was similar to that induced by UVC radiation but lower than that induced by X-radiation at equitoxic fluences/doses. The mutant frequency induced by PDT in WTK1 cells with either photosensitizer was much lower than that induced in murine lymphoblasts at equitoxic fluences. The TK6 and WTK1 cells did not differ in their sensitivity to the cytotoxic effects of PDT, but the level of PDT-induced apoptosis was greater in TK6 than in WTK1 cells. These results indicate that the mutagenicity of PDT varies in different types of cells and may be related to the repair capabilities as well as the p53 status of the cells.
Evans
H H
HH
Department of Radiology, Case Western Reserve University, Cleveland, OH 44106-4942, USA.
Horng
M F
MF
Ricanati
M
M
Deahl
J T
JT
Oleinick
N L
NL
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D002460:Cell Line; D004249:DNA Damage; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects / Q000528:radiation effects; D051379:Mice; D009154:Mutation; D018462:Photobiology; D010778:Photochemotherapy / Q000009:adverse effects*; D014466:Ultraviolet Rays / Q000009:adverse effects; D014965:X-Rays