Cycling hypoxia and radiosensitivity

Thesis

While chronic and acute hypoxia are well-studied components of radiobiology, research is emerging that consistently describes transient and cyclic patterns of hypoxia within the tumour microenvironment. The aim of this study is to better understand the effect that cyclic hypoxia could have on radiotherapy. Using the breast cancer cell line, MDA-MB-231, and cycling between ≤0.1 O₂ and 2% O₂, I investigated the biological response to cyclic versus chronic hypoxia. The impact of cyclic hypoxia on cell cycle, DNA damage and the expression of homologous recombination protein, Rad51, were investigated. Cyclic hypoxia was found to cause a significant reduction in clonogenic survival. Most importantly, cells exposed to cyclic hypoxia were found to be more radioresistant that cells irradiated after exposure to constant hypoxia (2% O₂), but were not as radioresistant as cells exposed to near anoxic levels (<0.1% O₂).

Authors: Zitter, R

• DOI: 10.5287/ora-xkqyvjpqo
• Type of award: MSc
• Level of award: Masters
• Awarding institution: University of Oxford
• Language: English
• Keywords: radiotherapy; radiosensitivity; breast cancer; hypoxia; cyclic hypoxia
• Subjects: Solid Tumours