DNA copy number variations of blood lymphocytes in people exposed to occupational irradiation as a possible marker of high radiosensitivity
This work presents the results of the study of blood lymphocytes DNA copy number variations (CNV) induced de novo in 46 healthy employees of the main facilities of the Siberian Group of Chemical Enterprises exposed to external irrradiation in a dose range of 100-300 mSv. We performed standard cytogenetic analysis in the entire examined group and carried out microarray studies of DNA samples by cytogenetic arrays: "Affymetrix" (USA) "CytoScan™ HD Array". As formed de novo CNV always recognized the mosaic deletion and amplification, which had 4 allele peaks. We considered only the CNV larger than 100 kbp. All of the examined presences were divided into two groups: control group (27 people) and experienced group (19 people). We have established that the long-term irradiation can induce CNV in blood lymphocytes. We have identified at least one formed de novo CNV in blood lymphocytes in 19 of 46 workers. These 19 employees were included in the experimental group, the employees, without any de novo CNV (27 employees) were included in the control group. Total, we have found 39 induced de novo CNV of different types in the employees of the experimental group. There were 11 mosaic amplifications, 2 mosaic deletions, 21 deletion and 5 amplifications. Two employees had the mosaic deletions in 3 chromosome (the patient #1490 and #394). 26 CNV, affecting the structure of the allelic peaks and length > 100 kbp (21 deletions and 5 amplifications). We have identified 26 CNV larger than 100 kbp. The average size of induced de novo CNV, was 714±228 kbp (min - 101 kbp, max - 7,727 kbp). The size of the amplifications (including mosaic amplifications) was 1,333±514 kbp, the size of the deletions (including mosaic deletions) was 284±78 kbp (p-value = 0.02) by Wilcoxon - Mann - Whitney test). Our analysis suggests a very high level of radiosensitivity in individuals of the experimental group, considering the same dose of external irradiation in the control and experimental groups (р = 0.6785). The increased frequency of aberrant cells and paired chromosome fragments (based on routine cytogenetic analysis) in employees, which have induced de novo CNV (experimental group) compared with the control group, confirms that.
Keywords
вариации числа копий,
CNV,
цитогенетические аномалии,
индивидуальная радиочувствительность,
низкоинтенсивное радиационное воздействие,
микроматричный анализ,
copy number variation,
CNV,
cytogenetic abnormalities,
individual radiosensitivity,
low-intensity irradiation,
microarray analysisAuthors
| Litviakov Nikolai V. | Seversk Biophysical Research Centre of the Federal Medical-Biological Agency; Cancer Research Institute, Siberian Branch of the Russian Academy of Medical Sciences (Tomsk); Tomsk State University | nvlitv72@yandex.ru |
| Khalyuzova Maria V. | Seversk Biophysical Research Centre of the Federal Medical-Biological Agency; Tomsk State University | gedonna@yandex.ru |
| Takhauov Ravil M. | Seversk Biophysical Research Centre of the Federal Medical-Biological Agency; Siberian State Medical University (Tomsk) | trm@sbrc.ru |
| Sazonov Alexey E. | Seversk Biophysical Research Centre of the Federal Medical-Biological Agency; Siberian State Medical University (Tomsk) | sazonov_al@mail.ru |
| Isubakova Daria S. | Seversk Biophysical Research Centre of the Federal Medical-Biological Agency | purksung@mail.ru |
| Bronikovskaya Evgenia V. | Seversk Biophysical Research Centre of the Federal Medical-Biological Agency | innahot@sibmail.com |
| Albakh Elena N. | Seversk Biophysical Research Centre of the Federal Medical-Biological Agency | elen-albah@rambler.ru |
| Bolshakov Michael A. | Tomsk State University; Institute of High Current Electronics, Siberian Branch of the Russian Academy of Sciences (Tomsk) | mbol@ngs.ru |
| Korostelev Sergey A. | First Moscow State Medical University after I.M. Sechenov; GENOMED Company (Moscow) | korostelevsa@genomed.ru |
| Karpov Andrey B. | Seversk Biophysical Research Centre of the Federal Medical-Biological Agency; Siberian State Medical University (Tomsk) | kab@sbrc.ru |
Всего: 10
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