APOPTOSIS AND DELAYED EXPRESSION OF C-JUN AND C-FOS AFTER GAMMA-IRRADIATION OF JURKAT T-CELLS

The purpose of this study was to determine the role of radiation-induc ed expression of c-jun and c-fos in radiation-induced apoptosis of cel ls of the Jurkat T-cell line. Doses of 10-20 Gy caused a massive numbe r of cells to undergo apoptosis within the first 24 h. This was accomp anied by extensive increases in c-jun mRNA levels and moderate increas es in c-fos levels, both occurring at the time of onset of internucleo somal DNA fragmentation. Increased c-jun and c-fos expression was maxi mum at 8 h after irradiation with a 10-fold increase in c-jun and a 2- fold increase in c-fos mRNA levels. In comparison, stimulation of the Jurkat cells with PMA resulted in rapid induction of c-jun and c-fos w ithin 1 h. The late induction of c-jun and c-fos was not preceded by i nduction of tumor necrosis factor-alpha (TNF-alpha) or the bifunctiona l repair endonuclease and nuclear redox factor Ref-1; rather a slow de crease in Ref-1 mRNA levels was found over the first 24 h. Our results showed that radiation-induced c-jun and c-fos expression is a late re sponse in Jurkat cells, and is most likely a secondary effect not nece ssary for radiation-induced apoptosis, Furthermore, apoptosis was indu ced by the RNA synthesis inhibitor actinomycin D, which does not induc e c-jun or c-fos expression. This demonstrates that massive late induc tion of c-jun and c-fos is not a general requirement for apoptosis in Jurkat cells. (C) 1996 by Radiation Research Society