Hypoxia-induced radioresistance is independent of hypoxia-inducible factor-1A in vitro

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Title: Hypoxia-induced radioresistance is independent of hypoxia-inducible factor-1A in vitro
Authors: Arvold, Nils D.1, Guha, Neela2, Wang, Dongfang2, Matli, Mary2, Deen, Dennis F.1,3, Warren, Robert S.2 warrenr@surgery.ucsf.edu, Haas-Kogan, Daphne A.1,3
Source: International Journal of Radiation Oncology, Biology, Physics. May2005, Vol. 62 Issue 1, p207-212. 6p.
Subjects: Cerebral anoxia, Hypoxemia, Cell lines, Transcription factors
Abstract: Purpose: We sought to determine whether hypoxia-induced radioresistance is mediated by the transcription factor hypoxia-inducible factor-1a (HIF-1a). Methods and materials: We used 2 mouse embryonic fibroblast cell lines transformed with H-ras and TAg, 1 HIF-1a+/+ and the other HIF-1a-/-. Cell were exposed to either 95% air and 5% CO2 (normoxic conditions) or 0.2% O2, 94.8% N2, and 5% CO2 (hypoxic conditions) for 4 hours. Cells were then irradiated and subjected to clonogenic survival assays. Results: Whereas neither +/+ ras/TAg nor -/- ras/TAg cells expressed HIF-1a under normoxic conditions, hypoxia induced expression of HIF-1a only in +/+ ras/TAg cells, confirming the absence of HIF-1a in -/- ras/TAg cells. Clonogenic survival curves for +/+ ras/TAg and -/- ras/TAg cells under normoxia and hypoxia demonstrated that hypoxia increased radioresistance in both cell lines to the same degree. At 1-log cell kill, the +/+ ras/TAg and -/- ras/TAg cells had an identical oxygen enhancement ratio of 1.28 ± 0.09 and nearly identical oxygen enhancement ratios at 2-log cell kill. Conclusion: In our system of transformed mouse embryonic fibroblasts, hypoxia-mediated radiation resistance is independent of HIF-1a. [Copyright &y& Elsevier]
Copyright of International Journal of Radiation Oncology, Biology, Physics is the property of Pergamon Press - An Imprint of Elsevier Science and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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  Data: Hypoxia-induced radioresistance is independent of hypoxia-inducible factor-1A in vitro
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  Data: <searchLink fieldCode="AR" term="%22Arvold%2C+Nils+D%2E%22">Arvold, Nils D.</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Guha%2C+Neela%22">Guha, Neela</searchLink><relatesTo>2</relatesTo><br /><searchLink fieldCode="AR" term="%22Wang%2C+Dongfang%22">Wang, Dongfang</searchLink><relatesTo>2</relatesTo><br /><searchLink fieldCode="AR" term="%22Matli%2C+Mary%22">Matli, Mary</searchLink><relatesTo>2</relatesTo><br /><searchLink fieldCode="AR" term="%22Deen%2C+Dennis+F%2E%22">Deen, Dennis F.</searchLink><relatesTo>1,3</relatesTo><br /><searchLink fieldCode="AR" term="%22Warren%2C+Robert+S%2E%22">Warren, Robert S.</searchLink><relatesTo>2</relatesTo><i> warrenr@surgery.ucsf.edu</i><br /><searchLink fieldCode="AR" term="%22Haas-Kogan%2C+Daphne+A%2E%22">Haas-Kogan, Daphne A.</searchLink><relatesTo>1,3</relatesTo>
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  Data: <searchLink fieldCode="JN" term="%22International+Journal+of+Radiation+Oncology%2C+Biology%2C+Physics%22">International Journal of Radiation Oncology, Biology, Physics</searchLink>. May2005, Vol. 62 Issue 1, p207-212. 6p.
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  Data: <searchLink fieldCode="DE" term="%22Cerebral+anoxia%22">Cerebral anoxia</searchLink><br /><searchLink fieldCode="DE" term="%22Hypoxemia%22">Hypoxemia</searchLink><br /><searchLink fieldCode="DE" term="%22Cell+lines%22">Cell lines</searchLink><br /><searchLink fieldCode="DE" term="%22Transcription+factors%22">Transcription factors</searchLink>
– Name: Abstract
  Label: Abstract
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  Data: Purpose: We sought to determine whether hypoxia-induced radioresistance is mediated by the transcription factor hypoxia-inducible factor-1a (HIF-1a). Methods and materials: We used 2 mouse embryonic fibroblast cell lines transformed with H-ras and TAg, 1 HIF-1a+/+ and the other HIF-1a-/-. Cell were exposed to either 95% air and 5% CO2 (normoxic conditions) or 0.2% O2, 94.8% N2, and 5% CO2 (hypoxic conditions) for 4 hours. Cells were then irradiated and subjected to clonogenic survival assays. Results: Whereas neither +/+ ras/TAg nor -/- ras/TAg cells expressed HIF-1a under normoxic conditions, hypoxia induced expression of HIF-1a only in +/+ ras/TAg cells, confirming the absence of HIF-1a in -/- ras/TAg cells. Clonogenic survival curves for +/+ ras/TAg and -/- ras/TAg cells under normoxia and hypoxia demonstrated that hypoxia increased radioresistance in both cell lines to the same degree. At 1-log cell kill, the +/+ ras/TAg and -/- ras/TAg cells had an identical oxygen enhancement ratio of 1.28 ± 0.09 and nearly identical oxygen enhancement ratios at 2-log cell kill. Conclusion: In our system of transformed mouse embryonic fibroblasts, hypoxia-mediated radiation resistance is independent of HIF-1a. [Copyright &y& Elsevier]
– Name: AbstractSuppliedCopyright
  Label:
  Group: Ab
  Data: <i>Copyright of International Journal of Radiation Oncology, Biology, Physics is the property of Pergamon Press - An Imprint of Elsevier Science and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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        Value: 10.1016/j.ijrobp.2005.01.019
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        Text: English
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      – SubjectFull: Cerebral anoxia
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      – SubjectFull: Cell lines
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              Text: May2005
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