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MOLECULAR-GENETIC MECHANISMS APOPTOSIS AND CELLULAR AGING CHANGES IN CEREBROVASCULAR DISEASES AT THE LATE PERIOD AFTER RADIATION EXPOSURE
[Article in Ukrainian]
D. Bazyka, I. Ilyenko, K. Loganovsky, S. Chumak, O. Lyaskyvska,
O. Belyaev, O. Maznychenko
SI “National Research Center for Radiation Medicine, National Academy of Medical Sciences of Ukraine”, Kyiv
Expression of genes-regulators of apoptosis and telomere activity were studied in complex with peripheral blood lymphocytes number at different stages of apoptosis and relative telomere length in 37 patients with cerebrovascular pathology and cognitive dysfunction including 29 Chornobyl clean-up workers of 1986–1987 with doses from 13.2 to 2800 mSv and 8 non-exposed patients. Control group included 13 volunteers of same age without CVD. Clinical investigation was carried out with neurophysiological, neuro- and psychometrical scales FSS, EDSS, MMSE, GHQ-28, BPRS, IDA, SDS. Cellular studies included subset analysis, relative telomere length (RTL) by flow-FISH, apoptosis by Annexin V-test, gene expression by RT-PCR using 7900HT station. CD8+ cells changes were shown 22–24 years after exposure in dose interval from 40 to 2800 mSv. CD95+ fraction increase was not accompanied by changes at early and late apoptosis stages. Down-regulation was demonstrated for genes regulators of p53-mediated apoptosis: TP53, TP53I3 and FASLG; together with overexpression of BAX and CCND1 and downregulation of TERF1 and TERF2. After exposure below 250 mSv the decreased NK cell numbers could result in immune surveillance defect. Substantial TP53 downregulation in this dose interval is accompanied by TR53I3 and CCND1 upregulation.
Key words: telomere, apoptosis, gene expression, ionising radiation, Chornobyl, “Shelter” object.
Probl. Radiac. Med. Radiobiol. 2011. Issue 16. P. 107–119.
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