The purpose of this study was to determine the role of radiation-induced expression of c-jun and c-fos in radiation-induced apoptosis of cells of the Jurkat T-cell line. Doses of 10-20 Gy caused a massive number of cells to undergo apoptosis within the first 24 h. This was accompanied by extensive increases in c-jun mRNA levels and moderate increases in c-fos levels, both occurring at the time of onset of internucleosomal DNA fragmentation. Increased c-jun and c-fos expression was maximum 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 within 1 h. The late induction of c-jun and c-fos was not preceded by induction of tumor necrosis factor-alpha (TNF-alpha) or the bifunctional repair endonuclease and nuclear redox factor Ref-1; rather a slow decrease 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 response in Jurkat cells, and is most likely a secondary effect not necessary for radiation-induced apoptosis. Furthermore, apoptosis was induced by the RNA synthesis inhibitor actinomycin D, which does not induce c-jun or c-fos expression. This demonstrates that massive late induction of c-jun and c-fos is not a general requirement for apoptosis in Jurkat cells.