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Chemosensitization by misonidazole in CCNU-treated spheroids and tumours.
Misonidazole has been demonstrated to enhance the cytotoxicity of several common antineoplastic drugs in vitro and in vivo, and its mechanism of action as a chemosensitizer, though still unknown, is thought to be dependent upon hypoxia. We have used fluorescence-activated cell sorting to evaluate ch...
Autores principales: | , |
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Formato: | Texto |
Lenguaje: | English |
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Nature Publishing Group
1987
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2002149/ https://www.ncbi.nlm.nih.gov/pubmed/3663461 |
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author | Durand, R. E. Chaplin, D. J. |
author_facet | Durand, R. E. Chaplin, D. J. |
author_sort | Durand, R. E. |
collection | PubMed |
description | Misonidazole has been demonstrated to enhance the cytotoxicity of several common antineoplastic drugs in vitro and in vivo, and its mechanism of action as a chemosensitizer, though still unknown, is thought to be dependent upon hypoxia. We have used fluorescence-activated cell sorting to evaluate chemopotentiation by misonidazole as a function of cell position in V79 spheroids and KHT tumours. CCNU toxicity was enhanced in all cell subpopulations of both tumours and spheroids, with greater consistency than might be predicted on the basis of the known variations in oxygen tension. Further, both misonidazole and CCNU as single agents were preferentially toxic in the less well oxygenated regions of each system, arguing that differential toxicity cannot be implicated in the chemopotentiation observed. In fact, increased treatment toxicity did not necessarily lead to increased chemopotentiation, nor was potentiation directly related to the metabolism/binding of the misonidazole. Chemopotentiation in multicell systems thus appears to be a complex, multi-factorial process. |
format | Text |
id | pubmed-2002149 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 1987 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-20021492009-09-10 Chemosensitization by misonidazole in CCNU-treated spheroids and tumours. Durand, R. E. Chaplin, D. J. Br J Cancer Research Article Misonidazole has been demonstrated to enhance the cytotoxicity of several common antineoplastic drugs in vitro and in vivo, and its mechanism of action as a chemosensitizer, though still unknown, is thought to be dependent upon hypoxia. We have used fluorescence-activated cell sorting to evaluate chemopotentiation by misonidazole as a function of cell position in V79 spheroids and KHT tumours. CCNU toxicity was enhanced in all cell subpopulations of both tumours and spheroids, with greater consistency than might be predicted on the basis of the known variations in oxygen tension. Further, both misonidazole and CCNU as single agents were preferentially toxic in the less well oxygenated regions of each system, arguing that differential toxicity cannot be implicated in the chemopotentiation observed. In fact, increased treatment toxicity did not necessarily lead to increased chemopotentiation, nor was potentiation directly related to the metabolism/binding of the misonidazole. Chemopotentiation in multicell systems thus appears to be a complex, multi-factorial process. Nature Publishing Group 1987-08 /pmc/articles/PMC2002149/ /pubmed/3663461 Text en https://creativecommons.org/licenses/by/4.0/This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Research Article Durand, R. E. Chaplin, D. J. Chemosensitization by misonidazole in CCNU-treated spheroids and tumours. |
title | Chemosensitization by misonidazole in CCNU-treated spheroids and tumours. |
title_full | Chemosensitization by misonidazole in CCNU-treated spheroids and tumours. |
title_fullStr | Chemosensitization by misonidazole in CCNU-treated spheroids and tumours. |
title_full_unstemmed | Chemosensitization by misonidazole in CCNU-treated spheroids and tumours. |
title_short | Chemosensitization by misonidazole in CCNU-treated spheroids and tumours. |
title_sort | chemosensitization by misonidazole in ccnu-treated spheroids and tumours. |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2002149/ https://www.ncbi.nlm.nih.gov/pubmed/3663461 |
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