Problems of Radiation Medicine and Radiobiology

I. M. Ilienko, N. A. Golyarnik, O.V. Lyaskivska, O. A. Belayev, D. A. Bazyka

State Institution «National Research Center for Radiation Medicine of the National Academy of Medical Sciences of Ukraine», 53 Melnykova str., Kyiv, 04050, Ukraine

EXPRESSION OF BIOLOGICAL MARKERS INDUCED BY IONIZING RADIATION AT THE LATE PERIOD AFTER EXPOSURE IN A WIDE RANGE OF DOSES

Objective. To study radiation induced biological markers of the late period after exposure.
Subjects and methods. A study was performed in 235 Chornobyl accident male clean-up workers exposed in 1986– 1987 (doses of external exposure: (M ± SD: 419.48 ± 654.60; range 0.10–3,500 mSv); age 58,34 ± 6,57 years. Control group included 45 non-exposed subjects (mean age: 50.60 ± 5.37 (M ± SD). Gene expression was performed by RT-PCR on 7900HT Analyzer using TLDA for BCL2, CDKN2A, CLSTN2, GSTM1, IFNG, IL1B, MCF2L, SERPINB9, STAT3, TERF1, TERF2, TERT, TNF, TP53, CCND1 genes. Relative telomere length (RTL) was analysed by flow-FISH; immune cell subsets, γ-H2AХ and CyclinD1 expression by flow cytometry.
Results. A statistically significant and dose-dependent decrease in expression of the BCL2, SERPINB9, CDKN2A, and STAT3 genes was demonstrated in parallel to a dose-dependent overexpression of MCF2L and upregulation of TP53 (up to 100 mSv). IL1B expression was the highest in exposed to doses from 0.1 to 100 mSv with a negative correlation between at IL1B expression and CD19⁺3^-, CD3^-HLA^-DR⁺, CD4⁺8^- cell counts and CD4⁺/CD8⁺ ratio. Hyperexpression of TNF gene in doses above 100 mSv to 1,000 mSv was shown, and in higher doses a combination of TNF downregulation with increase in IFNG gene expression were demonstrated with correlations with numbers of CD3⁺16⁺56⁺ and CD25⁺ lymphocytes and inhibition of expression CLSTN2. An increased expression of γ-H2AХ and Cyclin D1 correlated to radiation dose, telomere shortening to age and concommittant pathology.
Conclusions. Cellular immunity, gene expression, telomere length, intracellular protein parameters are shown to be among perspective biological markers at a late period after radiation exposure.
Key words: ionising radiation, gene expression, γ-H2AХ, telomere length, Cyclin D1, Chornobyl.

Problems of radiation medicine and radiobiology.
2018;23:331_350. doi: 10.33145/2304-8336-2018-23-331-350.

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