EARLY RESPONSE GENE SIGNALING CASCADES ACTIVATED BY IONIZING-RADIATION IN PRIMARY HUMAN B-CELLS

We have used a panel of 13 protein kinase C-responsive immediate early gene probes to dissect the cellular signalling pathways activated by ionising gamma radiation in primary human B cells. Of these 13 genes, a delayed transient induction was observed for only 8: c-fos, c-jun, j un-B, jun-D, c-myc, ergI/krox 24 and two 'anonymous' genes, 3L3 and 19 A. Expression of c-myc and c-fos mRNAs was paralleled by the appearanc e of their encoded proteins suggesting that these oncoproteins may cou ple radiation signalling to cellular responses. Of three protein kinas e C-coupled transcription factors examined by gel retardation assay, ( AP1, NF kappa B, EgrI/Krox24) only NF kappa B and, to a lesser extent, AP1 was stimulated in response to irradiation. These observations are not obviously compatible with a simple model invoking protein kinase C in radiation signalling in primary B cells and suggest that the plei otropic effects of ionising radiation on this cell type are mediated t hrough a distinct cellular signalling cascade.