title: Induction of radioprotective peroxiredoxin-I by ionizing irradiation.
abstract: Results of this study indicate a radioprotective effect of peroxiredoxin-I. Peroxiredoxin-I is an antioxidant that scavenges hydroperoxides, whereas reactive oxygen species are the main mediators of ionizing radiation toxicity. We hypothesized that peroxiredoxin-I 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-I protein and mRNA expression. Rat C6 glioma cells were engineered to overexpress sense or antisense human peroxiredoxin-I using retroviral vectors. Clonogenic cell survival was used to assess radiosensitivities of the engineered cells. Ionizing radiation induced peroxiredoxin-I 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-I on radiation responses, C6 glioma cells were engineered to overexpress sense or antisense human peroxiredoxin-I. In clonogenic assays, cells overexpressing peroxiredoxin-I were more radioresistant. Cells transduced with antisense peroxiredoxin-I were marginally more sensitive to radiation toxicity. Irradiation can induce peroxiredoxin-I expression, and the increased peroxiredoxin-I may protect cells from further radiation damage. These results suggest that protection by peroxiredoxin-I may play an important role in the survival of glioma and colon cancer cells in patients undergoing radiation therapy.
authors.affiliation: Department of Radiation Oncology, Chang Gung Memorial Hospital, Chia-Yi, Taiwan.
authors.forename: Wen-Cheng
authors.initials: WC
authors.lastname: Chen
authors.forename: William H
authors.initials: WH
authors.lastname: McBride
authors.forename: Keisuke S
authors.initials: KS
authors.lastname: Iwamoto
authors.forename: Chad L
authors.initials: CL
authors.lastname: Barber
authors.forename: Chun-Chieh
authors.initials: CC
authors.lastname: Wang
authors.forename: Young-Taek
authors.initials: YT
authors.lastname: Oh
authors.forename: Yu-Pei
authors.initials: YP
authors.lastname: Liao
authors.forename: Ji-Hong
authors.initials: JH
authors.lastname: Hong
authors.forename: Jean
authors.initials: J
authors.lastname: de Vellis
authors.forename: Hungyi
authors.initials: H
authors.lastname: Shau
mesh_terms: D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D002470:Cell Survival / Q000528:radiation effects; D004307:Dose-Response Relationship, Radiation; D005818:Genetic Engineering; D005910:Glioma / Q000235:genetics; D019073:HT29 Cells; D006801:Humans; D010544:Peroxidases / Q000235:genetics / Q000378:metabolism* / Q000528:radiation effects*; D054464:Peroxiredoxins; D012333:RNA, Messenger / Q000528:radiation effects*; D011836:Radiation Tolerance; D011839:Radiation, Ionizing; D051381:Rats; D014407:Tumor Cells, Cultured
chemical_list: D012333:RNA, Messenger; D010544:Peroxidases; D054464:Peroxiredoxins