CHANGES IN GENE EXPRESSION ASSOCIATED WITH NON-CANCER EFFECTS OF THE CHORNOBYL CLEAN-UP WORKERS IN THE REMOTE PERIOD AFTER EXPOSURE

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 control group: 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 in peripheral 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 were found 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 an increase of expression of СSF2, TERF1, TERF2 genes was established. The detected changes demonstrate an activation of the antioxidative defense system in patients with CHD, while AH is associated with the expression of genes of angiogenesis 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-up workers with BPP. Expression of TP53 and GSTM1 (gene, associated with the glutathione system) was significantly upregulated 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 the remote 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. Key words: gene expression, somatic pathology, radiation, Chornobyl.