| Paclitaxel-induced modification of the effects of radiation and alterations in the cell cycle in normal and tumor mammalian cells. | |
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MedLine Citation:
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PMID: 9728657 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The cytotoxicity of paclitaxel (taxol) is associated mainly with block in G2/M phase, the most radiosensitive phase of the cell cycle. Nevertheless, taxol-induced modification of the effects of radiation may vary from clear sensitization to subadditivity. Therefore, this effect was studied in relation to drug-induced alterations in the distribution of cells in the phases of the cell cycle in tumor cells (EMT-6 and OV-1063) and normal skin fibroblasts. Cell survival was evaluated with two colorimetric assays. The cell cycle was evaluated by FACS analysis of doubly-labeled cells. The radiosensitivity of the different cells studied was similar, apart from the less radiosensitive human fibroblasts. However, their dose- and time-dependent sensitivity to taxol varied significantly. After 24 h exposure of EMT-6 cells to taxol (IC50 approximately 20 nM), the fraction of cells in G2/M phase increased, the fraction in S phase decreased, and the proportion of possibly apoptotic cells with subdiploid and subtetraploid DNA content increased; this coincided with radiosensitization. In OV-1063 cells (IC50 approximately 3 nM), the drug-induced G2/M-phase block was most pronounced, but the combined effect with radiation was merely additive. In human fibroblasts (IC50 approximately 35 nM), a minimal G2/M-phase block with no change in the S phase and a massive elevation of apoptotic cells with subdiploid DNA content was accompanied by a subadditive combined effect with radiation. Six hours of exposure to taxol increased the fraction of cells in S phase in both nonsynchronized and S-phase-synchronized human fibroblasts (G1 phase approximately 65%, S phase approximately 13%). This was accompanied by a pronounced subadditive effect of the combined treatment. However, in G1-phase synchronized human fibroblasts (G1 phase > or =90%, S phase approximately 3%), only the fraction of cells in G2/M phase was slightly elevated, with a merely additive response to the combined treatment. The differences in the response to the combined treatment between slowly and rapidly proliferating cells in relation to modifications in the cell cycle are discussed. |
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Authors:
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R Gorodetsky; L Levdansky; I Ringel; A Vexler |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Radiation research Volume: 150 ISSN: 0033-7587 ISO Abbreviation: Radiat. Res. Publication Date: 1998 Sep |
Date Detail:
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Created Date: 1998-09-10 Completed Date: 1998-09-10 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 0401245 Medline TA: Radiat Res Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 283-91 Citation Subset: IM; S |
Affiliation:
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Sharett Institute of Oncology, Hadassah University Hospital, Jerusalem, Israel. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Antineoplastic Agents, Phytogenic / pharmacology* Cell Cycle / radiation effects* Cell Division / drug effects, radiation effects Cell Survival / drug effects, radiation effects Cells, Cultured / drug effects, radiation effects Dose-Response Relationship, Drug Dose-Response Relationship, Radiation Fibroblasts / drug effects, radiation effects Humans Interphase / drug effects, radiation effects Mice Paclitaxel / pharmacology* Radiation-Sensitizing Agents / pharmacology* S Phase / drug effects, radiation effects Time Factors |
| Chemical | |
Reg. No./Substance:
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0/Antineoplastic Agents, Phytogenic; 0/Radiation-Sensitizing Agents; 33069-62-4/Paclitaxel |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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