The role of p53 in gemcitabine-mediated cytotoxicity and radiosensitization
dc.contributor.author | Hough, Amanda M. | en_US |
dc.contributor.author | Chen, Mei | en_US |
dc.contributor.author | Lawrence, Theodore S. | en_US |
dc.date.accessioned | 2006-09-08T19:58:13Z | |
dc.date.available | 2006-09-08T19:58:13Z | |
dc.date.issued | 2000-04 | en_US |
dc.identifier.citation | Chen, Mei; Hough, Amanda M.; Lawrence, Theodore S.; (2000). "The role of p53 in gemcitabine-mediated cytotoxicity and radiosensitization." Cancer Chemotherapy and Pharmacology 45(5): 369-374. <http://hdl.handle.net/2027.42/42100> | en_US |
dc.identifier.issn | 0344-5704 | en_US |
dc.identifier.uri | https://hdl.handle.net/2027.42/42100 | |
dc.identifier.uri | http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=retrieve&db=pubmed&list_uids=10803919&dopt=citation | en_US |
dc.description.abstract | Purpose : We compared the cytotoxic and radiosensitizing effects of gemcitabine (2′,2′-difluoro-2′-deoxycytidine, dFdCyd), a clinically valuable radiosensitizer, in colon cancer RKO cells which differed in their p53 status. The parental RKO cells, RKO-P, contain wild-type p53 protein. In RKO-E6 cells, the p53 function has been disrupted by transfection of the cells with the human papillomavirus type-16 E6 gene. Results : We found that the RKO-P cells were significantly more sensitive to dFdCyd-mediated cytotoxicity and apoptosis than RKO-E6 cells (IC 10 39.3 ± 5.3 n M and 62.0 ± 6.9 n M , respectively). The cytotoxic effect of dFdCyd in RKO-P cells was accompanied by induction of the proapoptotic protein Bax at the time when p53 was induced. In contrast, similar treatment of RKO-E6 cells with dFdCyd resulted in only limited expression of Bax, suggesting that the cytotoxic effect of dFdCyd was mediated, in part, by a p53-dependent apoptosis pathway. We also studied the effect of dFdCyd on radiation sensitivity. We found that at minimally cytotoxic concentrations dFdCyd failed to radiosensitize either RKO-P or RKO-E6 cells, whereas at cytotoxic concentrations equal sensitization was produced. Finally, we assessed the influence of dFdCyd on cell cycle distribution. We found that dFdCyd synchronized RKO-P cells, whereas synchrony was not produced in p53-disrupted RKO-E6 cells. Conclusion : These results suggest that p53 status may influence dFdCyd-mediated apoptosis, cytotoxicity, and cell cycle progression but do not support an important role for p53 in radiosensitization. | en_US |
dc.format.extent | 295904 bytes | |
dc.format.extent | 3115 bytes | |
dc.format.mimetype | application/pdf | |
dc.format.mimetype | text/plain | |
dc.language.iso | en_US | |
dc.publisher | Springer-Verlag; Springer-Verlag Berlin Heidelberg | en_US |
dc.subject.other | Legacy | en_US |
dc.subject.other | Key Words Apoptosis | en_US |
dc.subject.other | Radio-sensitization | en_US |
dc.subject.other | P53 | en_US |
dc.subject.other | Gemcitabine | en_US |
dc.title | The role of p53 in gemcitabine-mediated cytotoxicity and radiosensitization | en_US |
dc.type | Article | en_US |
dc.subject.hlbsecondlevel | Chemical Engineering | en_US |
dc.subject.hlbsecondlevel | Biological Chemistry | en_US |
dc.subject.hlbsecondlevel | Radiology | en_US |
dc.subject.hlbsecondlevel | Chemistry | en_US |
dc.subject.hlbtoplevel | Engineering | en_US |
dc.subject.hlbtoplevel | Science | en_US |
dc.subject.hlbtoplevel | Health Sciences | en_US |
dc.description.peerreviewed | Peer Reviewed | en_US |
dc.contributor.affiliationum | Department of Radiation Oncology, University of Michigan Medical Center, 1500 E. Medical Center Drive, Ann Arbor, MI 48109-0010, USA Tel.: +1-734-6479955; Fax: +1-734-7637371, US | en_US |
dc.contributor.affiliationum | Department of Radiation Oncology, University of Michigan Medical Center, 1500 E. Medical Center Drive, Ann Arbor, MI 48109-0010, USA Tel.: +1-734-6479955; Fax: +1-734-7637371, US | en_US |
dc.contributor.affiliationum | Department of Radiation Oncology, University of Michigan Medical Center, 1500 E. Medical Center Drive, Ann Arbor, MI 48109-0010, USA Tel.: +1-734-6479955; Fax: +1-734-7637371, US | en_US |
dc.contributor.affiliationumcampus | Ann Arbor | en_US |
dc.identifier.pmid | 10803919 | en_US |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/42100/1/280-45-5-369_00450369.pdf | en_US |
dc.identifier.doi | http://dx.doi.org/10.1007/s002800051004 | en_US |
dc.identifier.source | Cancer Chemotherapy and Pharmacology | en_US |
dc.owningcollname | Interdisciplinary and Peer-Reviewed |
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