At present, there is a lack in the understanding of how antioxidants impact radioprotection. The cellular redox balance is maintained through a number of antioxidant enzymes such as heme oxygenase 1, superoxide dimutase, catalase, and glutathione. Oxidative stress and ionizing radiation activate transcriptional factors such as AP-1, NF-kB, and NRF-2 and PI-3K, PKC, and MAPK signaling cascades resulting in the induction of cellular antioxidants. Exploring the effects of ionizing radiation on antioxidant expression at the cellular level is essential before these pathways can be used to enhance radioprotection. We hypothesize that there is a hierarchal response to oxidative stress, inflammation, and cellular death in response to radiation dose. In addition to characterizing the antioxidant expression, we will explore the potential of modifying these redox responses in terms of their radioprotective effects. This project aims to improve the understanding of antioxidants in response to ionizing radiation and will clarify the importance of these mechanisms for radioprotection. ? ? ?
| McDonald, J Tyson; Kim, Kwanghee; Norris, Andrew J et al. (2010) Ionizing radiation activates the Nrf2 antioxidant response. Cancer Res 70:8886-95 |
