Transcriptional response to ionizing radiation in lymphocyte subsets.
Human lymphocyte subpopulations differ in their cellular responses to ionizing radiation. To shed light on the molecular basis of this effect, we characterized the transcriptional response to 1 Gy X-rays of CD4+ T lymphocytes. Of 18,433 genes tested, 102 were modulated more than 1.5-fold. The majority of the strongly activated genes were p53 targets involved in DNA repair and apoptosis. The expression of three of these genes was further tested by quantitative RT-PCR in lymphocyte subpopulations [CD4+ and CD8+ T, CD19+ B, CD56+ natural killer cells and peripheral blood lymphocytes (PBLs)] from ten adult donors. In contrast to DDB2, TNFRSF10B and BAX were differentially modulated among the subpopulations and the PBLs, being more activated in irradiated CD19+ B and CD8+ T lymphocytes. The level of BAX activation in the various subpopulations correlated with the sensitivity of the cells to radiation, suggesting its possible role in the differential radiosensitivity of hematopoietic cell subsets.
Mori
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Laboratory of Radiobiology and Microbiology, Belgian Nuclear Research Centre (SCK.CEN), Boeretang 200, Mol 2400, Belgium. mmori@sckcen.be
Benotmane
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MA
Tirone
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Hooghe-Peters
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EL
Desaintes
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C
D000328:Adult; D017209:Apoptosis; D015496:CD4-Positive T-Lymphocytes / Q000528:radiation effects*; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000528:radiation effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D011836:Radiation Tolerance; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics; D016176:T-Lymphocyte Subsets / Q000528:radiation effects*; D014158:Transcription, Genetic / Q000528:radiation effects; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D051028:bcl-2-Associated X Protein
C494826:BAX protein, human; C117669:DDB2 protein, human; D004268:DNA-Binding Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D018124:Receptors, Tumor Necrosis Factor; C505639:TNFRSF10B protein, human; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein