title: Overexpression of TP53, TP53I3 and BIRC5, alterations of gene regulation of apoptosis and aging of human immune cells in a remote period after radiation exposure.
abstract: OBJECTIVE
  To identify a contributive role of changes in gene regulation of apoptosis and telomere length at tran scriptional and translational levels to the formation of radiation induced effects in immune system.
  
  
  METHODS
  Study groups included 310 Chornobyl (Chornobyl) cleanup workers (dose of external expo sure (360.82 ± 32.3) mSv; age 58.9 ± 0.6 (M ± SD) years) and control (n = 77; age (52.9 ± 0.64) (M ± SD) years). Expression of CD95, phosphatidylserine receptors, bcl2 and p53 proteins was studied by flow cytometry; the relative expression (RQ) of BAX, BIRC5, FASLG, MADD, MAPK14, TP53, TP53I3, TERT, TERF1, TERF2 genes was performed using 7900 HT Fast RT PCR System and TagMan technology. Relative telomere length (RTL) was quantified by flow FISH assay.
  
  
  RESULTS
  Dose dependent deregulation of apoptosis was shown at transcriptional level (TP53, TP53 I3, BAX, BIRC5, FASL genes) and translational level (bcl 2 and p53 proteins) with blocking entry to apoptosis, dose dependent activation of anti apoptotic proteins and TP53 mediated expression of genes inhibitors of apoptosis. After exposure below 100 mSv a decrease in TERT gene RQ was associated with shortened telomeres, after exposure to doses over 500 mSv the TERT RQ and RTL increase were associated with imbalance in TERF1 and TERF2 genes expression.
  
  
  CONCLUSIONS
  Our study demonstrates a presence of subsequent changes in gene expression, regulatory proteins pres entation, telomere length and distribution of cells by the stages of apoptosis in a late period after radiation expo sure from low dose range to doses over 500 mSv. Results of the study contribute to the basic concepts on the late biological effects in immune system.
authors.affiliation: State Institution National Research Center for Radiation Medicine of the National Academy of Medical Sciences of Ukraine, Melnykov str., 53, Kyiv, 04050, Ukraine.
authors.forename: I N
authors.initials: IN
authors.lastname: Ilienko
authors.affiliation: State Institution National Research Center for Radiation Medicine of the National Academy of Medical Sciences of Ukraine, Melnykov str., 53, Kyiv, 04050, Ukraine.
authors.forename: D A
authors.initials: DA
authors.lastname: Bazyka
mesh_terms: D017209:Apoptosis / Q000528:radiation effects*; D016922:Cellular Senescence; D005786:Gene Expression Regulation; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D047908:Intracellular Signaling Peptides and Proteins; D011518:Proto-Oncogene Proteins; D000069079:Radiation Exposure; D000077022:Survivin; D016159:Tumor Suppressor Protein p53
chemical_list: C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D047908:Intracellular Signaling Peptides and Proteins; D011518:Proto-Oncogene Proteins; D000077022:Survivin; C495901:TP53 protein, human; C411296:TP53I3 protein, human; D016159:Tumor Suppressor Protein p53
keywords: Chornobyl; apoptosis; gene expression; radiation; telomeres