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

• Published in: International journal of radiation oncology, biology, physics Vol. 62; no. 1; pp. 207 - 212
• Main Authors: Arvold, Nils D., Guha, Neela, Wang, Dongfang, Matli, Mary, Deen, Dennis F., Warren, Robert S., Haas-Kogan, Daphne A.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.05.2005
• Subjects: Animals; Cell Hypoxia - physiology; Cell Line, Transformed - metabolism; Cell Line, Transformed - radiation effects; Fibroblasts - metabolism; Fibroblasts - radiation effects; HIF-1; Hypoxia; Hypoxia-Inducible Factor 1, alpha Subunit; Mice; Oxygen enhancement ratio; Radiation resistance; Radiation Tolerance - physiology; Transcription Factors - metabolism; Oxygen enhancement ratio; HIF-1; Radiation resistance; Hypoxia
• ISSN: 0360-3016; 1879-355X
• DOI: 10.1016/j.ijrobp.2005.01.019

Purpose: We sought to determine whether hypoxia-induced radioresistance is mediated by the transcription factor hypoxia-inducible factor-1α (HIF-1α). Methods and materials: We used 2 mouse embryonic fibroblast cell lines transformed with H- ras and TAg, 1 HIF-1α +/+ and the other HIF-1α −/−. Cell were exposed to either 95% air and 5% CO 2 (normoxic conditions) or 0.2% O 2, 94.8% N 2, and 5% CO 2 (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-1α under normoxic conditions, hypoxia induced expression of HIF-1α only in +/+ ras/TAg cells, confirming the absence of HIF-1α 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-1α.