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618.19 . . 1, . . 1, . . 1, . . 2, . . 쳿 ...

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˲ ISSN 2304 8336. 㳿 = Problems of radiation medicine and radiobiology. 2014. . 19.

618.19

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. TERF1, TERF2 TERT in situ . 258 , ( 222800 ) 78 . ʳ .

. c 100250 250500 (MSD: 15,8 50,27; p 0,02; 15,890,33; p 0,02; :

17,210,23). , (RTL) : TERF2 , TERF1; TERT. 500 TERT TERF1 TERF2 RTL , , . ( = 0,03) MMSE RTL, .

. TERF2, TERT TERF1 500 .

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D. A. Bazyka1, I. N. Ilyenko1, K. N. Loganovsky1, M. A. Benotmane2, S. A. Chumak1 1 State Institution National Research Center for Radiation Medicine of the National Academy of Medical Sciences of Ukraine, Melnykov str., 53, Kyiv, 04050, Ukraine Radiobiology Unit, Institute for Environment, Health and Safety, Belgian Nuclear Research Centre, SCK CEN, Belgium TERF1 and TERF2 downregulate telomere length in cognitive deficit at the late period after low dose exposure Purpose to explore the role of radiation dose on gene regulation of telomere length and its influence on the patho genesis of cerebrovascular neurocognitive deficit at the remote period of low dose irradiation as a result of the Chornobyl accident.

Materials and methods. We performed a study of TERF1, TERF2 and TERT genes expression (GE) by RT PCR, and relative telomere length (RTL) by flow FISH in 258 clean up workers of Chornobyl accident divided by radiation dose groups (range 222800 mSv) and 78 controls with vascular cognitive deficit. Detailed psychometric interviews were performed to obtain quantitative data on the stage of cognitive deficit.

Results. Statistically significant telomere shortening was demonstrated in groups of clean up workers with radiation doses in 100250 mSv and 250500 mSv range (subsequently M SD: 15.

85 0.27; p 0.02; 15.89 0,33; p 0.02; con trol: 17.21 0,23). A decrease in RTL was in parallel to radiation dose increase and overexpression of negative telomere length regulators: TERF2 genes and, to a lesser extent TERF1; the opposite tendency was demonstrated for TERT GE. In exposed over 500 mSv a significant TERT overexpression was combined with decreased TERF1 and TERF2 GE, and absence of significant RTL changes in comparison with clean up workers exposed to lower doses indicating a certain independ ency between gene expression and telomere length changes and possible threshold effects at this dose range. Analysis of the group of exposed in comparison with non exposed demonstrated a significant decrease (p = 0.03) both of the mean MMSE and RTL parameters suggesting influence of previous exposure.

Conclusion. This study shows parallel changes in decline of cognitive function and telomere length and differences in TERF2, TERT and TERF1 gene regulation at the late period after low dose and over 500 mSv exposure.

Key words: telomeres, low dose radiation, cognitive deficit, gene expression, TERF1, TERF2, TERT, Chornobyl.

Problems of radiation medicine and radiobiology. 2014;19:170 185.

   

˲ͲͲ ˲ ISSN 2304 8336. 㳿 = Problems of radiation medicine and radiobiology. 2014. . 19.

   

˲ͲͲ ˲ ISSN 2304 8336. 㳿 = Problems of radiation medicine and radiobiology. 2014. . 19.

   

˲ͲͲ ˲ ISSN 2304 8336. 㳿 = Problems of radiation medicine and radiobiology. 2014. . 19.

   

˲ͲͲ ˲ ISSN 2304 8336. 㳿 = Problems of radiation medicine and radiobiology. 2014. . 19.

   

(3)

   

3 ³ Table 3 Relative telomere length in peripheral blood leukocytes of examination groups

   

1. TERF1, TERF2, TERT 2527 (M SD) A ; B RQ TERF2; C RQ TERF1; D RQ TERT Figure 1.

Telomere length and gene expression in Chornobyl clean up workers 2527 years after radiation exposure (M+SD) Xaxis exposure groups; Yaxis: A relative telomere length; B RQ for TERF2; C RQ for TERF1; D RQ for TERT gene

   

˲ͲͲ ˲ ISSN 2304 8336. 㳿 = Problems of radiation medicine and radiobiology. 2014. . 19.

2. MMSE, (A) RTL (B) Figure 2.

Dependence between cognitive deficit according to the MMSE, age (A) and RTL (B) in clean up workers of Chornobyl accident 3. MMSE RTL , (M SD) Figure 3. Mean MMSE and RTL in clean up workers vs the age standardized group of non exposed (M+SD)

   

˲ͲͲ ˲ ISSN 2304 8336. 㳿 = Problems of radiation medicine and radiobiology. 2014. . 19.

   



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See discussions, stats, and author profiles for this publication at: http://www.researchgate.net/publication/277311242 ᒺ . (Study of. TECHNICAL REPORT DECEMBER 2013 DOI: 10.13140/RG.2.1.1966.8647 READS 5 AUTHORS, INCLUDING: Andrey A. Kovalchuk Natalia Kovalchuk Uzhhorod National University Uzhhorod National University...

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