Early response gene signalling cascades activated by ionising radiation in primary human B cells.

Abstract

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, jun-B, jun-D, c-myc, ergI/krox 24 and two 'anonymous' genes, 3L3 and 19A. Expression of c-myc and c-fos mRNAs was paralleled by the appearance of their encoded proteins suggesting that these oncoproteins may couple radiation signalling to cellular responses. Of three protein kinase C-coupled transcription factors examined by gel retardation assay, (AP1, NF kappa B, EgrK/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 pleiotropic effects of ionising radiation on this cell type are mediated through a distinct cellular signalling cascade.