Differential cell photosensitivity following porphyrin photodynamic therapy.
Experiments were performed to determine if differences in porphyrin photosensitivity could be observed for cells with varying efficiency in DNA damage repair, as well as for cells which make up components of the vasculature. Photofrin II is undergoing current clinical evaluation for photodynamic therapy of solid tumors, and therefore the retention, dark toxicity, and photosensitizing effects of this drug on human DNA repair-deficient fibroblasts (ataxia telangiectasia and xeroderma pigmentosum) were compared to normal human fibroblasts. In addition, bovine cells of endothelial, smooth muscle, and fibroblast origin were compared for porphyrin retention, toxicity, and photosensitivity. All human fibroblasts exhibited porphyrin-induced dark toxicity, but there were no significant differences in photosensitization or porphyrin retention for any of these cell lines. However, bovine endothelial cells were considerably more photosensitive than smooth muscle or fibroblast cells treated under identical conditions. All bovine cells accumulated similar levels of porphyrin, and therefore the increased sensitivity of the endothelial cells was not due to differences in porphyrin retention. These results provide additional evidence that nuclear damage and/or repair is not a dominant factor in the cytotoxicity induced by porphyrin photosensitization. In addition, these results indicate that endothelial cell photosensitivity may play a role in the vascular damage observed following photodynamic therapy.
Gomer
C J
CJ
Clayton Ocular Oncology Center, Children's Hospital, Los Angeles, California 90027.
Rucker
N
N
Murphree
A L
AL
D000818:Animals; D002417:Cattle; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004260:DNA Repair; D017323:Dihematoporphyrin Ether; D006414:Hematoporphyrin Photoradiation; D006415:Hematoporphyrins / Q000494:pharmacology*; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism; D010778:Photochemotherapy
D006415:Hematoporphyrins; D008077:Lipoproteins, LDL; D017323:Dihematoporphyrin Ether