Induction of radioprotective peroxiredoxin-I by ionizing irradiation

Results of this study indicate a radioprotective effect of peroxiredoxin-1. Peroxiredoxin-1 is an antioxidant that scavenges hydroperoxides, whereas reactive oxygen species are the main mediators of ionizing radiation toxicity. We hypothesized that peroxiredoxin-1 might be induced by cellular exposure to radiation and act to protect them against its cytotoxic effects. Western blot and Northern blot analyses were used to assess peroxiredoxin-1 protein and mRNA expression. Rat C6 glioma cells were engineered to overexpress sense or antisense human peroxiredoxin-1 using retroviral vectors. Clonogenic cell survival was used to assess radiosensitivities of the engineered cells. Ionizing radiation induced peroxiredoxin-1 protein and mRNA expression in human HT29 colon cancer and rat C6 glioma cells in a dose- and time-dependent manner over a 24 hr period. To determine the effect of peroxiredoxin-1 on radiation responses, C6 glioma cells were engineered to overexpress sense or antisense human peroxiredoxin-1. In clonogenic assays, cells overexpressing peroxiredoxin-1 were more radioresistant. Cells transduced with antisense peroxiredoxin-1 were marginally more sensitive to radiation toxicity. Irradiation can induce peroxiredoxin-1 expression, and the increased peroxiredoxin-1 may protect cells from further radiation damage. These results suggest that protection by peroxiredoxin-1 may play an important role in the survival of glioma and colon cancer cells in patients undergoing radiation therapy. (C) 2002 Wiley-Liss, Inc.