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Title: Impact of chronic blood viral infection on lymphocyte telomere length in Chornobyl clean-up workers in a remote period after radiation exposure.
Author: Ilienko IM, Lyaskivska OV, Belayev OA, Pleskach OY, Shinkarenko VI, Bazyka DA.
Journal: Probl Radiac Med Radiobiol; 2017 Dec; 22():372-381. PubMed ID: 29286521.
Abstract:
OBJECTIVE: To assess whether telomere length in lymphocytes of Chornobyl clean up workers at a late period 30 years after the exposure to ionizing radiation is influenced by a chronic blood viral infection and to determine role of viral carriage in cellular senescence. PATIENTS AND METHODS: Study group included 70 Chornobyl cleanup male workers 30 years after exposure {doses of external exposure (602.67 ± 114.19) mSv (M ± m); age (59.75 ± 0.82) yrs}. Relative telomere length (RTL) was analysed by fluorescence in situ hybridization and flow cytometry, immune cell subsets by standard combinations of monoclonal antibodies (CD45/14, CD3/19, CD4/8, CD3/HLADR, CD3/16/56, TCRγδ) and flow cytometry; antiviral immunity was performed determining the chronic phase antibodies to viruses: Hepatitis C (HCV), Cytomegalovirus (CMV), Toxoplasma gondii (TOX), Herpes simplex (HSV) and Epstein Barr virus (EBV VCA IgG and EBV NA IgG). The object of the study was peripheral blood (PB) of clean up workers. RESULTS: RTL changes were associated at the group level with the carrier state of the viral infection. RTL shortening was demonstrated as a significant difference between the groups (M ± SD) (HCV negative 15.27 ± 3.35, HCV posi tive 13.09 ± 3.05, p < 0.08, n = 12/52) or as a tendency (CMV negative 15.99 ± 5.41, CMV positive 14.86 ± 3.46 (M ± SD), p < 0.57, n = 11/53; HSV negative 17.01 ± 1.35, HSV positive 14.79 ± 3.80, p < 0.33, n = 13/51; TOX neg ative 15.94 ± 3.41, TOX positive 14.30 ± 3.81(M ± SD), p < 0.23, n = 27/37). These unidirectional changes can be associated with premature early cell aging of immune cells. To the contrary the significant RTL elongation was demonstrated in the group of EBV NA chronic carriers (EBV NA negative 11.25 ± 3.02 (M ± SD), EBV NA positive 16.15 ± 3.08 (M ± SD), p < 0.001, n = 15/49). CONCLUSION: The study confirmed the assumption on a relationship existing between the telomere length, chronic viral infection and late effects in immune cells. The changes of telomeres length on the background of immune dys function may be a sign of cellular aging, and concomitant chronic blood viral infection such as Hepatitis C, Epstein Barr viruses carriage could form a background for an error prone DNA reparation system as a factor of accumulation of pathological conditions, including malignant transformation. Meta. Otsinyty vplyv khronichnoï virusnoï infektsiï na pokaznyk vidnosnoï dovzhyny telomer limfotsytiv peryfe rychnoï krovi (PK) uchasnykiv likvidatsiï naslidkiv avariï (LNA) na ChAES u viddalenyy̆ period pislia oprominennia (30 rokiv potomu) ta vyznachyty rol' virusnogo nosiy̆stva u rozvytku pryskorenogo klitynnogo starinnia. Materialy i metody. Osnovna grupa obstezhennia vkliuchala 70 uchasnykiv LNA na ChAES cholovichoï stati, u viddaleno mu periodi pislia oprominennia – 30 rokiv potomu {doza zovnishn'ogo oprominennia skladala (602,67 ± 114,19) mZv (M ± m), vik (59,75 ± 0,82) rokiv}. Analiz provodyly zalezhno vid naiavnosti abo vidsutnosti antytil do khronichnoï fazy virusnoï infektsiï. Vyznachennia vidnosnoï dovzhyny telomer (relative telomere length – RTL) limfotsytiv PK provodyly za dopomogoiu flow FISH metodu (protochno tsytometrychna fluorestsentna gibrydyzatsiia in situ), subpo puliatsiï imunokompetentnykh klityn doslidzhuvaly z vykorystanniam protochnoï tsytometriï (FacsCalibur, BD) i stan dartnykh kombinatsiy̆ monoklonal'nykh antytil (CD45/14, CD3/19, CD4/8, CD3/HLADR, CD3/16/56, TCRγδ); vyznachen nia statusu protyvirusnogo imunitetu provodyly za dopomogoiu imunofermentnogo analizu, zokrema vyznachaly an tytila do khronichnoï fazy zakhvoriuvannia, a same do virusu gepatytu S (VGS), tsytomegalovirusnoï infektsiï (TsMV), toksoplazmy gondiï (TOKS), virusu prostogo gerpesu (VPG) ta virusu Epshtey̆n Barr (VEB VCA IgG ta VEB NA IgG). Ob’iekt doslidzhennia – PK uchasnykiv LNA na ChAES.Rezul'taty. Skorochennia vidnosnoï dovzhyny telomer pov’iazane z nosiy̆stvom virusnoï infektsiï na grupovomu rivni. Statystychno dostovirni zminy pokaznyka RTL bulo prodemonstrovano mizh doslidnymy grupamy (M ± SD) (VGS negatyvna 15,27 ± 3,35, VGS pozytyvna 13,09 ± 3,05, p < 0,08, n = 12/52) ta vyznacheno tendentsiiu (TsMV negatyv na 15,99 ± 5,41, TsMV pozytyvna 14,86 ± 3,46 (M ± SD), p < 0,57, n = 11/53; VPG negatyvna 17,01 ± 1,35, VPG pozytyv na 14,79 ± 3,80, r < 0,33, n = 13/51; TOKS negatyvna 15,94 ± 3,41, TOKS pozytyvna 14,30 ± 3,81 (M ± SD), r < 0,23, n = 27/37). Tsi odnospriamovani zminy mozhut' buty pov’iazani z peredchasnym starinniam imunokompetentnykh klityn. Opozytni zminy bulo prodemonstrovano v grupi uchasnykiv LNA na ChAES z nosiy̆stvom VEB NA. Vyznacheno statys tychno dostovirne pidvyshchennia pokaznyka RTL porivniano z grupoiu uchasnykiv LNA na ChAES z vidsutnistiu antytil do khronichnoï fazy VEB NA (EBV NA negatyvna 11,25 ± 3,02 (M ± SD), EBV NA pozytyvna 16,15 ± 3,08 (M ± SD), r <0,001, n = 15/49).Vysnovky. Doslidzhennia pidtverdylo prypushchennia pro zv’iazok mizh dovzhynoiu telomer limfotsytiv peryferych noï krovi, khronichnoiu virusnoiu infektsiieiu ta piznimy radioindukovanymy efektamy v imunokompetentnykh klity nakh. Zminy dovzhyny telomer na tli imunnoï dysfunktsiï mozhut' buty oznakoiu klitynnogo starinnia, a suputnia khronichna virusna infektsiia, taka iak virus gepatytu S i virus Epshtey̆n Barr, mozhe stvoriuvaty pidґruntia dlia «po mylkovoï» reparatsiï DNK, stvoriuiuchy umovy dlia zloiakisnoï transformatsiï.

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