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-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.
Syljuåsen
R G
RG
Department of Radiation Oncology, University of California, Los Angeles 90095, USA.
Hong
J H
JH
McBride
W H
WH
D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects*; D015152:Blotting, Northern; D019757:Carbon-Oxygen Lyases; D002460:Cell Line; D002470:Cell Survival; D004260:DNA Repair; D004273:DNA, Neoplasm / Q000302:isolation & purification / Q000528:radiation effects; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase; D003609:Dactinomycin / Q000494:pharmacology; D004307:Dose-Response Relationship, Radiation; D004587:Electrophoresis, Agar Gel; D005720:Gamma Rays; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000528:radiation effects*; D016762:Genes, fos / Q000528:radiation effects*; D016758:Genes, jun / Q000528:radiation effects*; D006801:Humans; D007700:Kinetics; D009687:Nuclear Proteins / Q000096:biosynthesis; D013601:T-Lymphocytes; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D004273:DNA, Neoplasm; D009687:Nuclear Proteins; D014409:Tumor Necrosis Factor-alpha; D003609:Dactinomycin; D019757:Carbon-Oxygen Lyases; C085108:APEX1 protein, human; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase; D013755:Tetradecanoylphorbol Acetate