Early gene expression profile in mouse brain after exposure to ionizing radiation.
Acute changes in the gene expression profile in mouse brain after exposure to ionizing radiation were studied using microarray analysis. RNA was isolated at 0.25, 1, 5 and 24 h after exposure to 20 Gy and at 5 h after exposure of the whole brain of adult mice to 2 or 10 Gy. RNA was hybridized onto 15K cDNA microarrays, and data were analyzed using GeneSpring and Significant Analysis of Microarray. Radiation modulated the expression of 128, 334, 325 and 155 genes and ESTs at 0.25, 1, 5 and 24 h after 20 Gy and 60 and 168 at 5 h after 2 and 10 Gy, respectively. The expression profiles showed dose- and time-dependent changes in both expression levels and numbers of differentially modulated genes and ESTs. Seventy-eight genes were modulated at two or more times. Differentially modulated genes were associated with 12 different classes of molecular function and 24 different biological pathways and showed time- and dose-dependent changes. The change in expression of four genes (Jak3, Dffb, Nsep1 and Terf1) after irradiation was validated using quantitative real-time PCR. Up-regulation of Jak3 was observed in another mouse strain. In mouse brain, there was an increase of Jak3 immunoreactivity after irradiation. In conclusion, changes in the gene profile in the brain after irradiation are complex and are dependent on time and dose, and genes with diverse functions and pathways are modulated.
Mahmoud-Ahmed
Ashraf S
AS
Department of Radiation Oncology, Sunnybrook and Women's College Health Sciences Centre, University of Toronto, Toronto, Ontario, M4N 3M5 Canada.
Atkinson
Shelley
S
Wong
C Shun
CS
D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000528:radiation effects*; D004307:Dose-Response Relationship, Radiation; D004781:Environmental Exposure; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology* / Q000528:radiation effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D011829:Radiation Dosage; D011839:Radiation, Ionizing; D014018:Tissue Distribution
D009419:Nerve Tissue Proteins