Induction of radioprotective peroxiredoxin-I by ionizing irradiation.
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.
Chen
Wen-Cheng
WC
Department of Radiation Oncology, Chang Gung Memorial Hospital, Chia-Yi, Taiwan.
McBride
William H
WH
Iwamoto
Keisuke S
KS
Barber
Chad L
CL
Wang
Chun-Chieh
CC
Oh
Young-Taek
YT
Liao
Yu-Pei
YP
Hong
Ji-Hong
JH
de Vellis
Jean
J
Shau
Hungyi
H
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
D012333:RNA, Messenger; D010544:Peroxidases; D054464:Peroxiredoxins