Gene expression analysis of oxidative stress and apoptosis in proton-irradiated rat retina.
The aim of this study was to examine the induction of oxidative stress and apoptosis-associated gene expression profiles in retina after proton irradiation exposure at 0.5 to 4 Gy.


METHODS
One eye of each Sprague-Dawley rat (6 per group) was irradiated with a conformal proton beam to total doses of 0, 0.5, 1 and 4 Gy. Retinal tissues were isolated for characterization of gene expression profiles 6 hours after proton radiation.


RESULTS
For oxidative stress, many genes responsible for regulating the production of reactive oxygen species (ROS) were significantly up-regulated (Fmo2, Gpx2, Noxa1 and Sod3) compared to controls. Several important genes involved in the initiation or activation of apoptotic signaling pathways were significantly up-regulated following irradiation (Fas, Faslg, Trp63 and Trp73). TUNEL assay and caspase-3 immunocytochemical analysis revealed increased apoptotic immunoreactivity following irradiation.


CONCLUSIONS
The data revealed that exposure to proton radiation induced oxidative stress-associated apoptosis. In response to ionizing radiation, the expression of genes involved in pathways mediating apoptosis may be differentially regulated in different dose regimens.
Mao
Xiao W
XW
Department of Radiation Medicine, Radiation Research Laboratories, Loma Linda University and Medical Center, Loma Linda, CA 92350, USA. xmao@dominion.llumc.edu
Green
Lora M
LM
Mekonnen
Tsehay
T
Lindsey
Nathan
N
Gridley
Daila S
DS
D000818:Animals; D017209:Apoptosis / Q000528:radiation effects*; D018076:DNA, Complementary / Q000235:genetics / Q000528:radiation effects; D004307:Dose-Response Relationship, Radiation; D005065:Euthanasia; D015870:Gene Expression / Q000528:radiation effects; D020287:In Situ Nick-End Labeling; D008297:Male; D018384:Oxidative Stress / Q000528:radiation effects*; D016133:Polymerase Chain Reaction; D011522:Protons / Q000009:adverse effects*; D012313:RNA / Q000235:genetics / Q000528:radiation effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012160:Retina / Q000502:physiology / Q000528:radiation effects*; D015854:Up-Regulation / Q000528:radiation effects
D018076:DNA, Complementary; D011522:Protons; D012313:RNA