The Role of the p53 Tumor Suppressor in the Response of Human Cells to Photofrin-mediated Photodynamic Therapy
2000; Wiley; Volume: 71; Issue: 2 Linguagem: Inglês
10.1562/0031-8655(2000)0710201trotpt2.0.co2
ISSN1751-1097
AutoresZhimin Tong, Gurmit Singh, Andrew J. Rainbow,
Tópico(s)Cancer, Hypoxia, and Metabolism
ResumoPhotochemistry and PhotobiologyVolume 71, Issue 2 p. 201-210 The Role of the p53 Tumor Suppressor in the Response of Human Cells to Photofrin-mediated Photodynamic Therapy Zhimin Tong, Zhimin Tong Department of Biology, McMaster University, Hamilton, Ontario, Canada Hamilton Regional Cancer Centre, Hamilton, Ontario, CanadaSearch for more papers by this authorGurmit Singh, Gurmit Singh Department of Pathology, McMaster University, Hamilton, Ontario, CanadaSearch for more papers by this authorAndrew J. Rainbow, Corresponding Author Andrew J. Rainbow Department of Biology, McMaster University, Hamilton, Ontario, Canada Hamilton Regional Cancer Centre, Hamilton, Ontario, Canada Department of Pathology, McMaster University, Hamilton, Ontario, Canada *To whom correspondence should be addressed at: Department of Biology, McMaster University, Hamilton, Ontario L8S 4K1, Canada. Fax: 905-522-6066; [email protected]Search for more papers by this author Zhimin Tong, Zhimin Tong Department of Biology, McMaster University, Hamilton, Ontario, Canada Hamilton Regional Cancer Centre, Hamilton, Ontario, CanadaSearch for more papers by this authorGurmit Singh, Gurmit Singh Department of Pathology, McMaster University, Hamilton, Ontario, CanadaSearch for more papers by this authorAndrew J. Rainbow, Corresponding Author Andrew J. Rainbow Department of Biology, McMaster University, Hamilton, Ontario, Canada Hamilton Regional Cancer Centre, Hamilton, Ontario, Canada Department of Pathology, McMaster University, Hamilton, Ontario, Canada *To whom correspondence should be addressed at: Department of Biology, McMaster University, Hamilton, Ontario L8S 4K1, Canada. Fax: 905-522-6066; [email protected]Search for more papers by this author First published: 01 May 2007 https://doi.org/10.1562/0031-8655(2000)0710201TROTPT2.0.CO2Citations: 9AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat ABSTRACT Although there is evidence that the p53 tumor suppressor plays a role in the response of some human cells to chemotherapy and radiation therapy, its role in the response of human cells to photodynamic therapy (PDT) is less clear. In order to examine the role of p53 in cellular sensitivity to PDT, we have examined the clonogenic survival of normal human fibroblasts that express wild-type p53 and immortalized Li–Fraumeni syndrome (LFS) cells that express only mutant p53, following Photofrin-mediated PDT. The LFS cells were found to be more resistant to PDT compared to normal human fibroblasts. The D37 (LFS cells)/D37 (normal human fibroblasts) was 2.8 ± 0.3 for seven independent experiments. Although the uptake of Photofrin per cell was 1.6 ± 0.1-fold greater in normal human fibroblast cells compared to that in LFS cells over the range of Photofrin concentrations employed, PDT treatment at equivalent cellular Photofrin levels also demonstrated an increased resistance for LFS cells compared to normal human fibroblasts. Furthermore, adenovirus-mediated transfer and expression of wild-type p53 in LFS cells resulted in an increased sensitivity to PDT but no change in the uptake of Photofrin per cell. These results suggest a role for p53 in the response of human cells to PDT. Although normal human fibroblasts displayed increased levels of p53 following PDT, we did not detect apoptosis or any marked alteration in the cell cycle of GM38 cells, despite a marked loss of cell viability. In contrast, LFS cells exhibited a prolonged accumulation of cells in G2 phase and underwent apoptosis following PDT at equivalent Photofrin levels. The number of apoptotic LFS cells increased with time after PDT and correlated with the loss of cell viability. A p53-independent induction of apoptosis appears to be an important mechanism contributing to loss of clonogenic survival after PDT in LFS cells, whereas the induction of apoptosis does not appear to be an important mechanism leading to loss of cell survival in the more sensitive normal human fibroblasts following PDT at equivalent cellular Photofrin levels. REFERENCES 1 Fisher, A. M. R., A. L. Murphree, C. J. 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