Radiation-induced transcription factor activation in the rat cerebral cortex

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 NFκB in the rat brain. Materials and methods: Male Sprague-Dawley rats were irradiated with ¹³⁷Cs γ-rays at 3.8 Gy/min and the cerebral cortex was isolated at intervals up to 24 h. 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 NFκB. 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 10 Gy and then decreased after higher doses. In contrast, NFκB DNA-binding activity continued to increase out to at least 30 Gy. The levels of bFGF and p21(WAF-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.