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Radiation-induced transcription factor activation in the rat cerebral cortex
U Raju1, G J Gumin, P J Tofilon
1Department of Experimental Radiation Oncology, The University of Texas M. D. Anderson Cancer Center, Houston 77030, USA.
Purpose:
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.
Materials And 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.