The Bank of Biological Samples Representing Individuals Exposed to Long-Term Ionizing Radiation at Various Doses

Abstract

Collection and storage of biological specimens in biobanks aims to obtain and preserve samples of different kinds for biological and medical studies. Here we present a description of the Bank of Biological Materials (BBM) housed by the Seversk Biophysical Research Centre (SBRC; Seversk, Russia). The main goal of maintaining the BBM is to collect and store biological samples suitable for genetic studies of people exposed to long-term ionizing radiation. Currently, the collection includes 19,194 biological specimens obtained from 8105 donors, of whom 42.3% are diagnosed with malignant neoplasms, 28.7% are healthy residents of the city of Seversk, 18.8% are healthy employees of the Siberian Group of Chemical Enterprises (SGCE), and 10.2% are patients diagnosed with acute myocardial infarction. The donors were enrolled using the Regional Medical and Dosimetric Register database created by the SBRC. For each donor, DNA specimens were extracted from peripheral blood and tissues and cell suspensions for cytogenetic analysis were prepared routinely. The BBM's unique collection is suitable primarily for studies of individual radiosensitivity of humans (IRH), and genetic aspects of the pathophysiology of common human diseases, especially in populations exposed to long-term low-dose ionizing radiation.

Introduction

The decoding of the human genome and the rapid progress in molecular biology and genetics has facilitated elucidation of the pathophysiological mechanisms of the development of many human chronic diseases, as well as subclinical effects of various environmental factors, including ionizing radiation. These discoveries allow the prediction of a coming boom in the development of novel diagnostic tools, treatment approaches, and prevention strategies. Thus, a value of the collection and preservation of biological specimens from persons with known medical history and documented exposure to various environmental factors has become a paramount goal.^1–5

In 2002, the Bank of Biological Materials (BBM) was established at the Seversk Biophysical Research Center (SBRC) of the Russian Federal Medical and Biological Agency (FMBA) (Seversk, Russia). The main focus of the BBM is to supply researchers with biological samples to allow exploration of the long-term effects of low-intensity ionizing radiation, to study individual radiosensitivity of humans (IRH), and to validate relevant biomarkers of exposure and response to irradiation.

The primary pool of donors was the employees of the Siberian Group of Chemical Enterprises (SGCE), the world's largest nuclear industrial complex, and the residents of the city of Seversk, an industrial town located in immediate proximity to the SGCE. Since the beginning of its operations in 1952, when the SGCE produced the first batch of enriched uranium, and over subsequent years, when the first nuclear reactor I-1 was put into operation, the SGCE maintained the regional ionizing radiation records. No significant radiological accidents or other incidents have occurred, however the overall levels of ionizing radiation for large groups of the SGCE employees and Seversk's residents were higher than standard population norms during the entire operating period of the SGCE.

During 2000–2002, the SBRC initiated and implemented the Regional Medical and Dosimetric Register (RMDR) for both the SGCE employees and Seversk residents. The RMDR database contains the data describing levels of radiation exposure for all employees of the SGCE for the whole of its operating period and includes information for approximately 66,500 people. The RMDR database also records information about the causes of death of all residents of Seversk who died in the town and the causes of death of former SGCE employees, even if they had moved away from the Seversk region. Additionally, the database records include detailed information about all cases of malignant tumors (MT) and acute myocardial infarctions (AMI) among the SGCE employees and residents of Seversk for the period from 1950 to 2012. These two nosological groups were selected because of a traditional focus of the assessments of the effects of radiation exposure on the incidence of malignant neoplasms, and due to the increased understanding of the role of ionizing radiation on the development of non-malignant age-related pathology, with cardiovascular diseases being a model.

Materials and Methods

Collection and verification of information about SGCE employees recruited for the BBM

Personnel information

Informed consent was obtained for all study participants; the Ethical Committee of the Seversk Biophysical Research Centre approved the study protocol. Employees were identified based on individual registration cards, which are kept in the data system of the Personnel Department of the SGCE. Information regarding each person contains given and family names, date of birth, date of employment at the SGCE, the department, occupation, and the history of transferring from one department to another. Information was also collected regarding the date of dismissal and new place of employment. More detailed information concerning the professional route, transfer from one plant to another within the SGCE, and changes in occupation, were obtained from the data system of the Personnel Department of each SGCE plant.

Vital status

The addresses of all citizens over the age of 16 years were recorded on an address card at the respective registration office. Sometimes the cards contained data concerning the change in family name. Information about the date and cause of death was received from various sources. Information was recorded by the Personnel Department when employees died. Verification of the date and cause of death was also performed at the Morbid Anatomy department at the Clinical hospital #81 of FMBA (CH #81). In situations of death of former SGCE employees who had changed their place of residence, this verification was performed at the registration office of their new place of residence. Additionally, in response to inquiries, relatives sent information about the causes of death of persons who had left Seversk. Coding of causes of death was performed according to the International Classification of Diseases 10 (ICD-10) regardless of the year of death.

Doses of external radiation

Data on individual doses of external γ-radiation measured by film- and thermoluminescent dosimeters were obtained from the Department of Occupational, Nuclear, and Radiation Safety of the SGCE. Individual dosimetric control (IDC) of staff was conducted since the beginning of the main technological processes in 1953. From 1958 to 1998, the system monitoring the individual γ-radiation dose used film dosimeters, and thermoluminescent dosimeters were used from 1988 to 2003. Since 1998, the SGCE has used an automated system of personal dosimetry with thermoluminescent dosimeters. This automated system has completely replaced the old film and thermoluminescent dosimeters.

In accordance with the organizational regulations of dosimetric control, IDC is only performed in a workplace where the level of γ-radiation can reach 30% of the allowable dose of radiation exposure in a year. Therefore, not all persons included in the RDMR have data concerning IDC. The RMDR contains information about individual doses for SGCE employees for each year of work, and the total accumulated dose for the entire period of work. Until now, external dose verification has not been performed. Currently, the RDMR database contains data regarding approximately 35,000 employees of primary production and mainly engaged in the production, out of which for 18,820 there are data on the obtained dose of external γ-irradiation.

The dose range in SGCE employees varies between 0.03 to 1800 millisieverts (mSv). However, the total cumulative dose of external radiation does not exceed 200 mSv in 89.94% of personnel.

For the population of Seversk citizens, the total equivalent dose to the whole body from 1970 to 1999 and the average annual effective dose from 2000 to 2005 were considerably lower than the maximum allowable doses (up to 1999, the upper dose limit was 500 mrem/year, and it has been 1 mSv/year since 2000).

Internal radiation

The information regarding the SGCE employees exposed to internal radiation has been obtained from the data provided by the Biophysical Laboratory of the Hygiene and Epidemiology Centre #81 of the FMBA. Systematic monitoring of the radionuclide content and level of radiation exposure was carried out from the beginning of 1960. The main method of radionuclide content evaluation in organisms is the indirect method based on analysis of the nuclear bioassay of natural excretions. The broad range of values for the ²³⁹Pu content that was accumulated in the body, and the small percentage of the surveyed persons made it difficult to perform direct assessment of the risk dependence based on the plutonium content or internal exposure dose for the different levels of exposure.

The SGCE employees underwent biophysical determination of ²³⁹Pu on the background of pentatsin and without pentatsin. The calculation of internal doses from ²³⁹Pu was carried out in accordance with the “Dose-2005” model, which is based on a system of differential equations describing the behavior of plutonium in the respiratory tract and extrapulmonary system.⁶ Equations have the following form: \documentclass{aastex}\usepackage{amsbsy}\usepackage{amsfonts}\usepackage{amssymb}\usepackage{bm}\usepackage{mathrsfs}\usepackage{pifont}\usepackage{stmaryrd}\usepackage{textcomp}\usepackage{portland, xspace}\usepackage{amsmath, amsxtra}\pagestyle{empty}\DeclareMathSizes{10}{9}{7}{6}\begin{document} \begin{align*} dq_{i} / dt = V (t) \cdot D_{i} + \mathop\sum_{i = 1}^{n} \lambda_{j , i} \cdot q_{i} - \mathop\sum_{j = 1}^{n} \lambda_{i , j \cdot q_{i}} , \tag{\rm Eq. 1}\end{align*} \end{document}

V(t), the speed of entrance of a nuclide into the organ (tissue);

q_i, q_j, the content of plutonium in i-th, j-th chambers;

λ_{j, i}, λ_{i, j}, constants of transmission from j-th chamber to i-th chamber and back.

Quantities of a nuclide in an organ (tissue) are obtained by solving the equations. The number of decays within a given time t is obtained by summarizing the system values obtained in the meantime. Transition of the number of decays to dosage units was carried out by well-known relations. Calculation of doses was carried out on the deposits in the major organs (lungs, liver, skeleton).

Sources of medical information

The main source of medical information is the archive of medical records of the SBRC. The archive contains approximately 135,242 entities, including more than 24,000 ambulatory records of former SGCE employees, autopsy reports from 1950 to 2012, and a journal of histological studies from 1950 to 2012. Additionally, the archive contains the medical records of more than 65,000 patients who were SGCE employees and Seversk residents and were undergoing diagnosis and treatment at the CH #81 for the following diseases: MT (solid cancers) (C00-C80), hemoblastoses (C81-C96), disorders of thyroid gland (E00-E07), congenital malformations (Q00-Q89), AMI (I21), acute stroke (intracerebral hemorrhage (I61) and cerebral infarction (I63)), and diabetes mellitus (E10-E14). The disease coding was carried according to the International Statistical Classification of Diseases and Related Health Problems: 10th Revision (http://www.who.int/classifications/icd/en/). Selection of these disease entities was based on their high impact on morbidity and mortality and on the need for in-depth studies concerning the role of ionizing radiation on the pathogenesis of these diseases and possible long-term stochastic effects of radiation of low intensity.

Additional sources of information include the medical documentation stored at CH #81 (current medical records of outpatients and hospitalized patients, as well as clinical laboratory journals), and the Regional Centre of Health (Tomsk) where SGCE employees are treated. CH #81 is the only major medical and preventive establishment that performs a full spectrum of medical assistance to the SGCE personnel and the population of the city of Seversk. Thus, the possibility of data loss is virtually eliminated.

Structure of the Biological Materials Bank

The BBM is a structural unit of the Laboratory of Genomic Medicine (LGM) of the SBRC and is split into the following subdivisions:

1. Healthy employees of SGCE

2. Healthy Seversk residents

3. MT patients (SGCE employees and Seversk residents)

4. AMI patients (SGCE employees and Seversk residents)

Methods of biological material collection

Sampling of biological material is performed only when donors have signed the informed consent. Voluntary agreement was written in accordance with Articles 30–33 of the Legislation Fundamentals of the Russian Federation dated 22.07.1993, #5487-1, and in accordance with Part 5 of the rules of Good Clinical Practice (GCP) of the International Conference on Harmonization (ICH). The list of potential donors to the BBM among healthy employees of SGCE was based on the targeted sampling from the RMDR database, and donors were invited to donate blood to the LGM. Information on patients with MT and patients with AMI was received from CH #81 after diagnosis of the disease. The blood sampling of MT patients was performed before special treatment procedures (chemotherapy, radiotherapy, surgery). The blood sampling of AMI patients was performed at a specialized department of CH #81 or at the LGM after discharge.

After blood samples and informed consent were obtained by the LGL staff, the donor was assigned a unique personal identification number (PIN) matching the PIN in the RMDR database. Only the manager of the LGM has access to the codification of the BBM database. Access to the RMDR data and the database of donors of the BBM, as well as levels of access for different users, were determined by a special documentation developed in accordance with Russian legislation and international protocols.

For preparation of cytogenetic suspensions, blood was drawn into a Vacuette test tube containing 7.9 mL of heparin. For extraction of nucleic acids, blood was drawn into a Vacuette tube containing 9.7 mL EDTA. Blood from the Vacuette tube containing EDTA was split into three numbered, plastic 1.5-mL Eppendorf tubes at the LGM. One tube was used for DNA extraction, and the remaining blood was stored at −80°C in the blood bank.

Tissue sampling of MN patients was performed during diagnostic procedures (biopsy) and surgery. Three samples were extracted from the surgery material:

1. tumor tissue

2. tissue from an area adjacent to the tumor

3. normal organ tissue distant from the tumor

After fixation in neutral formalin, all tissue samples were embedded into paraffin blocks by standard methods.⁷ Histological samples from each tissue sample were prepared. Tissue samples and histological preparations from each donor were stored together in individual plastic containers.

DNA isolation and quality assessment

DNA from EDTA blood was extracted by the standard phenol-chloroform technique with minor modifications.⁸

From 30 to 100 micrograms of DNA was obtained from 0.7 mL of the whole blood. The concentration and purity of the extracted DNA were measured using the NanoDrop-2000 spectrophotometer (Thermo Scientific, USA). The average concentration of DNA in the samples was 550±103 ng/μL with an A260/A280 index of 1.75–2.15 and an A260/A230 index of 1.60–2.31. DNA integrity was assessed by capillary electrophoresis using TapeStation instrument (Agilent Technologies, USA).

DNA from formalin-fixed paraffin-embedded tissues obtained by biopsy or surgery was also extracted using the phenol-chloroform method.

After isolation and assessment of qualitative and quantitative characteristics, all DNA samples were stored in ultra-low temperature freezers (MDF-U4186S; Sanyo, Japan) at a temperature of −80°C.

Cytogenetic preparations

Lymphocytes were obtained from the whole blood with heparin and subjected to a short-term culture on the day of the sampling. Cytogenetic suspensions were obtained and after the final fixation split into two parts, one of which was used to make cytogenetic preparations for the routine analysis of chromosomal aberrations, and the second part was poured into plastic 1.5-mL tubes and stored in a freezer at a cytogenetic suspension bank at −20°C.

All procedures were performed under sterile conditions using a laminar flow hood. Lymphocytes from peripheral blood were cultured in RPMI 1640 medium supplemented with 15% fetal calf serum and 40 mg/mL phytohemagglutinin (Sigma, USA). Culture flasks of 25 mL (TPP, USA) were placed in a dry-air thermostat at 37°C and cultured for 45 hours. Next, colchicine was added to a final concentration 0.06 mg/mL and the culture continued for another 3 hours. After 48 h of incubation, the cultures were washed in hypotonic solution (0.56% solution of KCl containing 0.95% sodium citrate), fixed by a mixture of ethanol and glacial acetic acid (3:1) and placed onto chilled, fat-free glass slides. Chromosomes were stained using the Giemsa method. For chromosome analysis, a Leica DM2500 microscope (Leica, Germany) was used. For each individual, 300 metaphases were analyzed.

Results and Discussion

Main components of the BBM

Since its inception in 2002, the SBRC has collected 19,194 biological specimens from 8106 donors, of whom 3393 (41.3%) are patients with MT, 2123 (25.8%) are healthy Seversk residents, 1801 (23.3%) are healthy SGCE employees, and 789 (9.6%) are AMI patients (Table 1).

Table 1.

Distribution of Biological Samples in Various Subdivisions of the Bank of Biological Materials of the Seversk Biophysical Research Centre

Biological sample	Healthy employees of SGCE	Healthy Seversk residents	MT patients	AMI patients	Total
Whole blood	1801	2123	932	789	5645
Tissue materials (tumor and normal tissues)	–	–	3481	–	3481
Blood and tissue DNA	2780	2123	1340	755	6998
Cytogenetic suspensions	2294	–	776	–	3070
Total	6875	4246	6529	1544	19194

The first subdivision of the biobank contained blood, cytogenetic suspensions, blood DNA, and blood RNA from healthy employees of SGCE. The second subdivision of the biobank contained samples of blood and blood DNA from healthy Seversk residents. In the third subdivision of the biobank, the following biological materials were collected from MT patients, SGCE employees, and Seversk residents: blood samples, cytogenetic suspensions, blood DNA, histological slides, samples of tumor and normal tissues (in FFPE blocks) obtained from diagnostic biopsy or surgery, and DNA samples extracted from normal and tumor tissues. The fourth subdivision of biobank contained blood and DNA samples isolated from blood leukocytes of patients with AMI who were SGCE employees and Seversk residents.

In total, the BBM contains 5645 preserved blood samples stored at −80°C and about 7000 samples of DNA. Cytogenetic suspensions are only available for the first and third subdivisions of the biobank.

Healthy employees of SGCE

At present, the BBM subdivision Healthy Employees of SGCE contains biological materials from 1801 donors (1188 men and 613 women). At the time of sample collection, the average age of the men was 55.7±8.9 years and the average age of the women was 59.2±9.04 years. The average duration of work at the SGCE for men was 27.44±0.40 years, and the average duration of work for women was 25.1±0.56 years. It is important to note that use of the term “healthy” indicated that donors of the bank did not have MT or AMI. Considering that most of the donors of the group were over 45 years, they most likely would not be considered healthy people in the usual sense of the word. The same specification concerns applied to the donors of the “Healthy Seversk residents” subdivision.

Regarding the RMDR database, annual updates of information on cases of MT and AMI among SGCE employees and Seversk residents are performed. This procedure allows exclusion of individuals with MT and AMI from banks of healthy donors. This is important in the analysis of the effects of radiation exposure. During the period 2002–2012 years, 61 healthy SGCE employees were subsequently identified as MT patients (different locations), in addition to 124 people identified as having AMI. Blood and DNA samples of these individuals have been moved to the appropriate subdivisions of the BBM.

Depending on the type of occupational exposure, healthy SGCE employees are divided into four groups: group 1 comprises 226 employees of the SGCE who have not been exposed to ionizing radiation and are generally used as a control; group 2 of 708 employees exposed only to external γ-radiation; group 3 of 100 employees exposed only to internal irradiation due to incorporated ²³⁹Pu; and group 4 of 767 employees exposed to combined (external and internal) irradiation. Thus, groups 2–4 included 1575 SGCE employees exposed long-term to occupational irradiation (Table 2).

Table 2.

External and Internal Irradiation Doses in Healthy Group of Donors Employed at SGCE

	Dose of external radiation, mSv
Dose of internal radiation, mSv	0	>0–20	>20–50	>50–100	>100–200	>200–350	>350–500	>500
0	226	266	96	85	96	68	44	53
0–0.1	40	199	50	7	5	3	2	1
0.1–0.5	13	45	52	35	19	8	3	1
0.5–1	9	19	22	22	17	10	2	1
1–5	24	27	23	32	35	21	7	5
5–10	14	10	9	10	20	30	7	8

The mean value of the external dose was 113.3±4.0 mSv, and the dose ranged from 0.0001 to 1620 mSv with the median of 66.74 mSv and the interquartile range of 15.89–104.74 mSv. Most donors received external irradiation at the ”low“ dose range of up to 200 mSv.

The average dose of internal exposure was 4.52±0.004 mSv, the median of 0.263 mSv and the interquartile range from 0.0001 to 1.303 mSv.

Healthy Seversk residents

The collection of this subdivision began in 2011. This group includes people unrelated to the SGCE employees who have not been exposed to ionizing radiation and have never been diagnosed with MT or AMI. Currently, it contains 2123 DNA samples from blood of healthy Seversk residents, of whom 397 donors are male, and 1726 donors are female. At the time of sample collection, the donor age ranged from 18 to 80 years, and the average age was 48.6±0.4 years. The average age of women was 48.3±0.5 years, and the average age of men was 50.2±1.2 years. At the same time, the information regarding radiation hazards and smoking status was obtained and we updated information regarding the donors parenting children with birth defects and cases of MT in donor's close relatives. Additionally, information was collected about donors with diseases such as chronic pulmonary diseases, cardiovascular diseases, gastrointestinal tract diseases, urinary system diseases, endocrine system diseases (e.g., thyroid, ovary, and prostate diseases), diabetes, bone and joint diseases, neurological diseases, and metabolic diseases.

Malignant tumor patients

This subdivision contains biological materials obtained from 3137 MT patients (1547 men and 1590 women). The average age of the disease onset was 63.3±0.68 years for men and 61.3±1.24 years for women. For 2347 patients, tumor and normal tissue samples in FFPE blocks (3481 samples) were collected. For 753 MT patients, blood samples, cytogenetic suspensions, and blood DNA were collected; for 141 of these MT patients, there are also samples of tumor and normal tissues.

A total of 2526 MT patients were not exposed to ionizing radiation. Of which, 851 patients (478 men and 373 women) were employees of the SGCE, and 1675 (607 men and 1068 women) were residents of Seversk who never worked at the SGCE.

Six hundred and eleven MT patients working at the SGCE (462 men and 149 women) were exposed to long-term occupational irradiation. Of these MT patients, 302 (222 men and 80 women) were exposed only to external irradiation, 95 patients (64 men and 31 women) were exposed only to internal irradiation, and 214 persons (176 men and 38 women) were exposed to combined irradiation Table 3 shows the distribution of donors according to tumor location.

Table 3.

Location of Primary Tumor in Donors with Malignant Disorders

				SGCE employees exposed to long-term occupational irradiation
				Type of irradiation
Tumor location	Diagnosis encoding^*	Seversk residents	SGCE employees unexposed to occupational irradiation	External irradiation	Internal irradiation	Combined irradiation
Cancer of esophagus	C15	39	22	6	2	3
Cancer of stomach	C16	245	118	49	14	32
Colon cancer	C18	203	65	34	15	18
Rectum cancer	C20	103	59	17	7	13
Cancer of bronchus and lungs	C34	52	50	22	8	14
Skin cancer	C44	120	67	30	5	14
Breast cancer	C50	199	85	20	3	12
Cancer of uterine cervix	C53	69	21	4	2	3
Cancer of uterus	C54	73	37	13	2	4
Ovarian cancer	C56	41	5	3	1	1
Prostate cancer	C61	22	29	21	6	17
Kidney cancer	C64	72	40	7	7	16
Cancer of urinary bladder	C67	41	25	11	13	2
Thyroid cancer	C73	27	21	7	2	2
Other localization	–	369	207	58	8	63

^* according to the International Statistical Classification of Diseases and Related Health Problems: 10th Revision

The minimal dose of external irradiation was 0.1 mSv, whereas the maximal dose was 234.5 mSv. The average dose was 129.1±10.9 mSv, whereas the median dose was 39.3 mSv and the interquartile range was 8.39–175.30 mSv.

The average dose of internal exposure was 4.193±0.0016 mSv, the median of −0.498 mSv and the interquartile range from 0.0001 to 2.319 mSv. The minimal dose of internal exposure was 0.0001 mSv, and the maximal dose was 86.704 mSv (one patient from this group had a high Plutonium body burden) (Table 4).

Table 4.

External and Internal Irradiation Doses in Donors with Malignant Tumors

	Dose of external radiation, mSv
Dose of internal radiation, mSv	0	>0–20	>20–50	>50–100	>100–200	>200–350	>350–500	>500
0	851	184	22	19	18	24	18	17
0–0.1	87	173	3	6	2	3	2	0
0.1–0.5	5	3	4	2	5	1	2	1
0.5–100	3	1	1	3	0	2	0	0

The table shows the number of persons with the specified doses of external and internal radiation.

Acute myocardial infarction patients

This subdivision contains the blood and blood DNA of 789 patients with acute myocardial infarction (AMI). The average age of the men was 60.82±0.47 years, and the average age of the women was 67.37±0.77 years.

Four hundred and sixty AMI patients (262 men and 198 women) were SGCE employees who were not exposed to irradiation. Three hundred and twenty nine AMI patients (285 men and 44 women) were SGCE employees who had long-term radiation exposure. Of these, 192 SGCE employees had only external exposure, whereas 41 SGCE employees had only internal exposure, and 96 SGCE employees had combined exposure (Table 5).

Table 5.

External and Internal Irradiation Doses in Donors with Acute Myocardial Infarction

	Dose of external radiation, mSv
Dose of internal radiation, mSv	0	>0–20	>20–50	>50–100	>100–200	>200–350	>350–500	>500
0	460	113	17	15	19	11	6	11
0–0.5	30	13	8	7	9	3	3	1
0.5–1	2	2	4	3	1	3	0	0
1–5	6	6	2	1	6	2	2	2
5–1000	3	1	2	5	1	7	1	1

The table shows the number of persons with the specified doses of external internal irradiation.

The minimal dose of external radiation was 0.0001 mSv, and the maximum dose was 946 mSv. The average external dose was 125.9±3.8 mSv, whereas the median dose was 47 mSv, and the interquartile range was 12.8–152.7 mSv. The average dose of internal radiation was 3.462±0.0009 mSv, while the minimal level was 0.0001 mSv, and the maximal level was 73.788 mSv (one patient from this group had a high Plutonium body burden). The median was 0.367 mSv and the interquartile range from 0.0001 to 2.021 mSv.

In addition to the dose of radiation exposure for each donor, the bank has updated information on the status of smoking and alcohol use, date of diagnosis, localization of infarct, concomitant diseases, physical activity, and metabolic syndromes, as well as the data from electrocardiograms at third and eighteenth days after AMI, the data from echocardiography, the data from scintigraphy and coronagraphy, the results of the measurement of the level of markers of myocardial necrosis, and basic biochemical parameters.

Conclusion

In summary, the Bank of Biological Materials of the SBRC provides a unique and virtually inexhaustible source of biological specimens for research aimed at revealing the molecular basis of IRH, for studies of the genetic mechanisms of pathogenesis of cancer and common human diseases under the exposure to long-term ionizing radiation in low-dose range, and for other research studies devoted to radiation and medical genetics.

The BBM is one of the world's largest repositories of biological specimens for people under long-term exposure to ionizing radiation. Of note, the BBM is constantly expanding and more samples and biological specimens of different types (e.g., RNA) are being added routinely.

Using the BBM, a number of research projects have been successfully carried out by our group.^9–11 Apparently, this is not an exhaustive list of possible applications of the BBM resource and a lot more can be done, especially in collaboration with other groups.

The BBM is a nonprofit division of the SBRC and is in the public domain for cooperation under the terms of the implementation of joint research projects. The samples can be provided for free to parties interested in collaborative research.

Footnotes

Acknowledgments

This work was supported by the Russian Foundation for Basic Research (#13-04-01970/14) and the Federal Medical and Biological Agency (#56.004.14.0).

Author Disclosure Statement

No conflicting financial interests exist.

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