A low-dose arsenic induced p53-mediated metabolic mechanism of radiotherapy protection [Cell Biology]

January 3rd, 2014 by Ganapathy, S., Xiao, S., Yang, M., Qi, M., Choi, D. E., Ha, C. S., Little, J. B., Yuan, Z.-M.

Radiotherapy is the current front line cancer treatment, but the resulting severe side effects often pose a significant threat to cancer patients, raising a pressing need for the development of effective strategies for radiotherapy protection. We exploited the distinct metabolic characteristics between normal and malignant cells for a metabolic mechanism of normal tissue protection. We show that low doses of arsenic induce HIF-1α, which activates a metabolic shift from oxidative phosphorylation to glycolysis resulting in increased cellular resistance to radiation. Of importance is that low-dose arsenic-induced HIF-1α requires functional p53, making the glycolytic shift limited to normal cells. Using tumor-bearing mice, we provide proof-of-principle for selective normal tissue protection against radiation injury.