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Title: CHANGES IN GENE EXPRESSION ASSOCIATED WITH NON-CANCER EFFECTS OF THE CHORNOBYL CLEAN-UP WORKERS IN THE REMOTE PERIOD AFTER EXPOSURE.
Author: Ilienko IM, Bazyka DA, Golyarnyk NA, Zvarych LM, Shvayko LI, Bazyka KD.
Journal: Probl Radiac Med Radiobiol; 2020 Dec; 25():456-477. PubMed ID: 33361854.
Abstract:
OBJECTIVE: to establish the connection of radiation-induced changes in gene expression with the realized pathology of the broncho-pulmonary and cardiovascular systems in Chornobyl clean-up workers. MATERIALS AND METHODS: We examined 314 male Chornobyl clean-up workers (main group; age (58.94 ± 6.82) years(M ± SD); min 33, max 79 years; radiation dose (411.82 ± 625.41) mSv (M ± SD); min 1.74, max 3600 mSv) with various nosological forms of cardiovascular and broncho-pulmonary pathology (BPP) and 50 subjects of the controlgroup: age (50.50 ± 5.73) years (M ± SD); min 41, max 67 years. The relative level of BCL2, CDKN2A, CLSTN2, GSTM1,IFNG, IL1B, MCF2L, SERPINB9, STAT3, TERF1, TERF2, TERT, TNF, TP53, CCND1, CSF2, VEGFA genes expression was determined inperipheral blood leukocytes by real-time PCR (7900 HT Fast Real-Time PCR System (Applied Biosystems, USA)). The«gene-disease» association was determined on statistical models stratified separately for each disease and gene.Logistic regression was used to calculate the odds ratio. RESULTS: Increased GSTM1 gene expression and no changes in angiogenesis-related VEGFA gene expression werefound in the main group of patients with coronary heart disease (CHD). It was established overexpression of TP53,VEGF and IFNG genes in the group of patients with arterial hypertension (AH). At combination of these diseases anincrease of expression of СSF2, TERF1, TERF2 genes was established. The detected changes demonstrate an activationof the antioxidative defense system in patients with CHD, while AH is associated with the expression of genes ofangiogenesis and immune inflammation. It was shown an increase in the expression of genes associated with apoptosis and kinase activity (BCL2, CLSTN2, CDKN2), immune inflammation (CSF2, IL1B, TNF) in Chornobyl clean-upworkers with BPP. Expression of TP53 and GSTM1 (gene, associated with the glutathione system) was significantlyupregulated in the group of individuals with chronic bronchitis, whereas in patients with chronic obstructive pulmonary disease, no increase was detected; the expression of SERPINB9 and MCF2L genes was downregulated. CONCLUSIONS: Changes in the expression of genes, associated with the development of somatic pathology in theremote period after irradiation, in particular the genes of the immune response and inflammatory reactions CSF2,IFNG, IL1B, TNF; expression of genes that regulate cell proliferation, aging and apoptosis TP53, BCL2, MCF2L, CDKN2A,SERPINB9, TERF1, TERF2, TERT; genes that regulate cell adhesion and angiogenesis CLSTN2, VEGF. Meta: vstanovyty zv’iazok radiatsiĭno-asotsiĭovanykh porushen' gennoï ekspresiï z realizovanoiu patologiieiubronkholegenevoï ta sertsevo-sudynnoï system v uchasnykiv likvidatsiï naslidkiv avariï (LNA) na ChAES.Materialy i metody. Obstezheno 314 uchasnykiv LNA na ChAES 1986–1987 rr. (osnovna grupa) cholovichoï stati zriznymy nozologichnymy formamy sertsevo-sudynnoï ta bronkholegenevoï patologiĭ ta 50 osib kontrol'noï grupy.Vikova kharakterystyka: osnovna grupa – (58,94 ± 6,82) rokiv (M ± SD); 33/79 rokiv (min/max), kontrol'nagrupa – (50,50 ± 5,73) rokiv (M ± SD); 41/67 rokiv (min/max). Dozy zovnishn'ogo oprominennia osib osnovnoïgrupy: (411,82 ± 625,41) mZv (M ± SD); 1,74/3600 mZv (min/max). Provedeno vyznachennia vidnosnogo rivniaekspresiï geniv: BCL2, CDKN2A, CLSTN2, GSTM1, IFNG, IL1B, MCF2L, SERPINB9, STAT3, TERF1, TERF2, TERT, TNF, TP53, CCND1,CSF2, VEGFA u leĭkotsytakh peryferychnoï krovi metodom polimeraznoï lantsiugovoï reaktsiï u real'nomu chasi (7900HT Fast Real-Time PCR System (Applied Biosystems, USA)). Vyznachennia asotsiatsiï «gen-zakhvoriuvannia» provedenona statystychnykh modeliakh, stratyfikovanykh okremo dlia kozhnogo zakhvoriuvannia ta gena. Logistychna regresiia bulavykorystana dlia rozrakhunku koefitsiientiv shansiv.Rezul'taty. V osib osnovnoï grupy, khvorykh na ishemichnu khvorobu sertsia vyiavleni pidvyshchennia ekspresiï genaGSTM1 ta vidsutnist' zmin gennoï ekspresiï VEGFA. V grupi khvorykh na gipertonichnu khvorobu vyznacheno giperekspresiiu geniv TP53, VEGFA ta IFNG. Pry poiednanni danykh zakhvoriuvan' vstanovleno pidvyshchennia ekspresiï genivCSF2, TERF1, TERF2. Vyiavleni zminy demonstruiut' vkliuchennia systemy okysnogo gomeostazu u khvorykh na ishemichnukhvorobu sertsia, todi iak gipertonichna khvoroba asotsiiuiet'sia z ekspresiieiu geniv angiogenezu ta imunnogo zapalennia.V uchasnykiv LNA na ChAES z bronkholegenevoiu patologiieiu vstanovleno zrostannia ekspresiï geniv, pov’iazanykh zapoptozom ta kinaznoiu aktyvnistiu (BCL2, CLSTN2, CDKN2A), imunnym zapalenniam (CSF2, IL1B, TNF); ekspresiia genaTP53 ta gena GSTM1, pov’iazanogo z systemoiu glutationu, bula dostovirno pidvyshchenoiu v grupi osib z khronichnymbronkhitom, todi iak u khvorykh na khronichne obstruktyvne zakhvoriuvannia legen' pidvyshchennia ne vyznachalosia;znyzhenoiu bula ekspresiia geniv SERPINB9 ta MCF2L.Vysnovky. Vyznacheno zminy ekspresiï geniv, asotsiĭovani z rozvytkom somatychnoï patologiï u viddalenomuperiodi pislia oprominennia, zokrema geniv imunnoï vidpovidi ta zapal'nykh reaktsiĭ CSF2, IFNG, IL1B, TNF; ekspresiïgeniv-reguliatoriv klitynnoï proliferatsiï, starinnia ta apoptozu TP53, BCL2, MCF2L, CDKN2A, SERPINB9, TERF1, TERF2,TERT; geniv-reguliatoriv klitynnoï adgeziï ta angiogenezu CLSTN2, VEGFA.

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