Ionizing radiation induces apoptotic cell death in human TcR-gamma/delta+ T and natural killer cells without detectable p53 protein.
The p53 tumor suppressor gene has been shown to be involved in programmed cell death, apoptosis, in murine immature thymocytes after treatment with ionizing radiation. Ionizing radiation also induces apoptosis in peripheral mature lymphocytes. In this work, we investigated the p53 participation in radiation-induced apoptosis in human peripheral blood lymphocytes (PBL) subpopulations. Exposure to gamma-irradiation resulted in an appreciable induction of apoptotic cell death in TcR-alpha/beta+ (CD4+ and CD8+) T cells, TcR-gamma/delta+ T cells, B cells and natural killer (NK) cells, as assessed by DNA fragmentation as well as the morphological characteristics. Importantly, it was found that there was a marked difference among PBL subpopulations as regards the induction of p53 protein by gamma-irradiation. Similar to previous observations for murine thymocytes, p53 induction in TcR-alpha/beta+ T cells and B cells after gamma-irradiation was evident by Western blot analysis. Radiation-induced apoptosis in TcR-alpha/beta+ T cells and B cells was efficiently inhibited by cycloheximide, indicating the requirement of de novo protein synthesis, including p53 protein, for radiation-induced apoptosis in both subpopulations. In marked contrast, no identifiable levels of p53 protein were induced in either TcR-gamma/delta+ T or NK cells after gamma-irradiation. In addition, it was demonstrated that radiation-induced cell death in TcR-gamma/delta+ T and NK cells could be prevented by interleukin-2, but not by cycloheximide. These results imply that radiation-induced lymphocytic apoptosis can be mediated by p53-dependent or -independent mechanisms.
Department of Pediatrics, School of Medicine, Kanazawa University, Ishikawa, Japan.
H
H
Seki
H
H
Kanegane
K
K
Iwai
A
A
Konno
K
K
Ohta
A
A
Yachie
N
N
Taniguchi
T
T
Miyawaki
D000328:Adult; D017209:Apoptosis / Q000528:radiation effects*; D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D004247:DNA / Q000378:metabolism; D006801:Humans; D007694:Killer Cells, Natural / Q000528:radiation effects*; D011839:Radiation, Ionizing; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000032:analysis*; D013601:T-Lymphocytes / Q000528:radiation effects*; D016159:Tumor Suppressor Protein p53 / Q000032:analysis / Q000502:physiology*
D016692:Receptors, Antigen, T-Cell, gamma-delta; D016159:Tumor Suppressor Protein p53; D004247:DNA; D003513:Cycloheximide