P53-DEPENDENT X-RAY-INDUCED MODULATION OF CYTOKINE MESSENGER-RNA LEVELS IN-VIVO

In vitro studies have shown that ionizing radiation can cause increase s in some cytokine mRNA levels and activation of the nuclear NF-kappa B and/or AP1 transcription factors which have been implicated in the t ranscriptional regulation of many cytokine genes. Thus, radiation-indu ced upregulation of cytokine mRNAs appeared to be in part a direct con sequence of transcription factor activation, To test this ill vitro mo del in vivo, the effects of whole-body X-irradiation (0-10 Gy) on cyto kine and other gene mRNA levels have been examined in mice. Increases and decreases in cytokine mRNA levels were detected in tissues which u nderwent an early wave of apoptosis (bone marrow and/or spleen), but n ot in more radioresistant tissues (kidney, liver, brain, and heart), S ome mouse strain-specific differences were observed, but none of the c hanges in mRNA level was detected in p53 -/- mice. As activation of th e NF-kappa B and AP1 transcription factors was not detected in early-( spleen) or late-(liver) responding tissues in 10 Gy X-irradiated p53 /+ mice in vivo, it is concluded that the modulation of cytokine gene expression in vivo is p53-dependent and indirectly associated with apo ptosis, (C) 1998 John Wiley & Sons, Ltd.