A radiation-induced adaptive response prolongs the survival of prion-infected mice.
Previously, it has been demonstrated that an "adaptive response" that includes the prevention, repair, and removal of oxidative damage can be evoked by radiation at dose rates substantially lower than those at which risks have been observed. The exact pathogenic mechanism of prion diseases is unknown, but circumstantial evidence suggests that oxidative stress plays a central role. Exposure of prion-infected mice to four 500 mGy/fraction doses of (60)Co γ-radiation administered every other day at a low dose rate (0.5 mGy/min) starting at 2 days before infection, 7 days postinfection (dpi), or 50 dpi significantly prolonged the survival of infected mice. The 500-mGy radiation treatments started at 50 dpi also significantly prolonged the symptom-free period of the disease and caused a significant delay in the rise of the 8-hydroxydeoxyguanosine concentration observed in the urine of nonirradiated infected mice at 98 dpi. The duration of the reduction in oxidative stress achieved by the radiation treatments was similar in length to the prolonged survival of the irradiated mice. This suggests that the adaptive response induced by low-dose whole-body radiation treatments prolongs the survival of prion-infected mice by reducing oxidative stress.
Plews
Margot
M
Prion Diseases Program, Public Health Agency of Canada, Winnipeg, MB R3E 3R2, Canada.
Simon
Sharon L R
SL
Boreham
Douglas R
DR
Parchaliuk
Debra
D
Wyatt
Heather
H
Mantha
Rebecca
R
Frost
Kathy
K
Lamoureux
Lise
L
Stobart
Michael
M
Czub
Stefanie
S
Mitchel
Ron E
RE
Knox
J David
JD
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000652:urine; D018450:Disease Progression; D007239:Infections / Q000503:physiopathology / Q000532:radiotherapy* / Q000652:urine; D051379:Mice; D008810:Mice, Inbred C57BL; D009425:Nesting Behavior / Q000528:radiation effects; D018384:Oxidative Stress / Q000528:radiation effects*; D011328:Prions; D011829:Radiation Dosage; D017382:Reactive Oxygen Species / Q000378:metabolism; D001743:Urinary Bladder / Q000378:metabolism* / Q000473:pathology / Q000528:radiation effects; D014916:Whole-Body Irradiation
D011328:Prions; D017382:Reactive Oxygen Species; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine