title: TERF1 and TERF2 downregulate telomere length in cognitive deficit at the late period after low-dose exposure.
abstract: 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 22-2800 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 100-250 mSv and 250-500 mSv range (subsequently M ± SD: 15.85 ± 0.27; p< 0.02; 15.89 ± 0,33; p< 0.02; control: 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 independency 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.
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. vkpand@ukr.net.
authors.forename: D A
authors.initials: DA
authors.lastname: Bazyka
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. vkpand@ukr.net.
authors.forename: I M
authors.initials: IM
authors.lastname: Ilyenko
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. vkpand@ukr.net.
authors.forename: K N
authors.initials: KN
authors.lastname: Loganovsky
authors.affiliation: Radiobiology Unit, Institute for Environment, Health and Safety, Belgian Nuclear Research Centre, SCK-CEN, Belgium.
authors.forename: M A
authors.initials: MA
authors.lastname: Benotmane
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. vkpand@ukr.net.
authors.forename: S A
authors.initials: SA
authors.lastname: Chumak
keywords: Chornobyl; TERF1; TERF2; TERT; cognitive deficit; gene expression; low-dose radiation; telomeres