Radiation-induced transcription factor activation in the rat cerebral cortex.
OBJECTIVE
To determine the effects of ionising radiation on the DNA-binding activity of the injury-related transcription factors AP-1, Sp-1, p53 and NFkappaB in the rat brain.


METHODS
Male Sprague-Dawley rats were irradiated with 137Cs gamma-rays at 3.8Gy/min and the cerebral cortex was isolated at intervals up to 24h. Nuclear protein extract of the cerebral cortex was analysed by electrophoretic mobility shift assay for DNA-binding activity of AP-1, Sp-1, p53 and NFkappaB. In addition, total RNA was extracted from the cerebral cortex and subjected to northern analysis.


RESULTS
The DNA-binding activity of each of the transcription factors increased in a time- and dose-dependent manner after irradiation. Maximum increase in the activity of AP-1, Sp-1, and p53 DNA binding was seen after exposure to 10Gy and then decreased after higher doses. In contrast, NFkappaB DNA-binding activity continued to increase out to at least 30Gy. The levels of bFGF and p21WAF-1 mRNA increased after irradiation, suggesting an increase in the transactivating activity of AP-1, Sp-1, and p53.


CONCLUSIONS
These data indicate that the response of the CNS to irradiation includes the activation of a similar set of transcription factors as previously observed after other types of insults.
Raju
U
U
Department of Experimental Radiation Oncology, The University of Texas M. D. Anderson Cancer Center, Houston 77030, USA.
Gumin
G J
GJ
Tofilon
P J
PJ
D000818:Animals; D002540:Cerebral Cortex / Q000502:physiology* / Q000528:radiation effects*; D004268:DNA-Binding Proteins / Q000502:physiology / Q000528:radiation effects; D008297:Male; D016328:NF-kappa B / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016329:Sp1 Transcription Factor / Q000502:physiology; D018808:Transcription Factor AP-1 / Q000502:physiology; D014157:Transcription Factors / Q000502:physiology* / Q000528:radiation effects; D014158:Transcription, Genetic; D016159:Tumor Suppressor Protein p53 / Q000502:physiology
D004268:DNA-Binding Proteins; D016328:NF-kappa B; D016329:Sp1 Transcription Factor; D018808:Transcription Factor AP-1; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53