Hypoxia-induced radioresistance is independent of hypoxia-inducible factor-1A in vitro.
Int J Radiat Oncol Biol Phys
; 62(1): 207-12, 2005 May 01.
Article
em En
| MEDLINE
| ID: mdl-15850923
ABSTRACT
PURPOSE:
We sought to determine whether hypoxia-induced radioresistance is mediated by the transcription factor hypoxia-inducible factor-1alpha (HIF-1alpha). METHODS AND MATERIALS We used 2 mouse embryonic fibroblast cell lines transformed with H-ras and TAg, 1 HIF-1alpha+/+ and the other HIF-1alpha-/-. 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-1alpha under normoxic conditions, hypoxia induced expression of HIF-1alpha only in +/+ ras/TAg cells, confirming the absence of HIF-1alpha 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-1alpha.
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Base de dados:
MEDLINE
Assunto principal:
Tolerância a Radiação
/
Fatores de Transcrição
/
Hipóxia Celular
Idioma:
En
Ano de publicação:
2005
Tipo de documento:
Article