Vol 68, No 2 (2023)
Radiation Biology
5-10
Effect of a Humic-Fulvic Acid Preparation on the Quantitative Yield of Residual γH2AX Foci and Proliferative Activity in Irradiated Human Mesenchymal Stromal Cells
Abstract
Purpose: To evaluate the influence of a humic-fulvic acid substance on the quantitative yield of residual foci of the DNA double-strand break (DSB) repair protein-marker - phosphorylated histone H2AX (γH2AX) and proliferation activity in a culture of human mesenchymal stromal cells (MSCs) 24, 48, and 72 h after exposure to X-ray radiation at doses of 2, 4 and 10 Gy.
Material and methods: Through 24 hours after incubation of MSCs with a substance of humic-fulvic acids (Humic Complex, OOO Sistema-BioTechnologies, Russia) at a dilution of 1/1000. Cells were irradiated on an X-ray biological device RUB RUST-M1 at a voltage of 200 kV, beam current 2×5 mA, aluminum filter 1.5 mm, absorbed dose rate 0.85 Gy/min. Immunocytochemical staining was used to quantify the residual γH2AX foci and the percentage of proliferating cells using antibodies to γH2AX and Ki-67 (a marker protein for cell proliferation), respectively. Statistical analysis of the obtained data was carried out using the statistical software package Statistica 8.0 (StatSoft). To assess the significance of differences between samples, Student’s t-test was used.
Results and conclusion: The conducted studies showed that on the cell model used and under the above experimental conditions, the humic-fulvic acid substance does not affect the efficiency of repair of radiation-induced DNA DSBs, however, it significantly reduces the proliferation activity of both irradiated and non-irradiated MSCs. It is advisable to conduct detailed studies of the molecular and cellular mechanisms of the antiproliferative effect of humic and fulvic acids.
11-15
The Effect of Drugs for Normalize Blood Supply and Trophism of Irradiated Tissues, as well as a Broad-Spectrum Antibiotic on the Course of Severe Local Radiation Injuries in Rats
Abstract
Purpose: To study in the experiment the therapeutic efficacy of drugs that normalize blood supply and trophism of irradiated tissues, as well as a complex broad-spectrum antibiotic, for the course of severe local radiation lesions to justify the clinical use of these drugs in this pathology.
Material and methods: Wistar-Kyoto inbred rats were exposed to local X-rays in the ilio-lumbar region of the back at a dose of 110 Gy (tube voltage 30 kV, current 6.1 mA, Al filter 0.1 mm thick), at a dose rate of 20.1 Gy / min. Irradiation field area was 8.5 cm2. Radiation exposure caused the formation of long-term (up to 3.5–4 months) non-healing radiation ulcers of the skin without a critical radiation load on the underlying tissues. For the treatment of radiation lesions, an antibiotic was used – levotetrasulfin forte, as well as drugs that affect the blood supply and trophism of irradiated tissues – pentoxifylline and detralex. The drugs were administered daily both in isolation from each other and together during the period (from the 21st to the 42nd or from the 28th to the 48th day after irradiation), when the radiation ulcer formed and its gradual healing began. The everity of radiation skin lesions and the effects of therapy were assessed in dynamics by clinical manifestations and using planimetry.
Results: It was found that the separate use of drugs in the treatment of severe local radiation lesions was not very effective. However, with the combined administration of drugs, a noticeable increase in the rate of healing of radiation ulcers was revealed. Thus, it was shown that with the joint administration of pentoxifylline (intraperitoneal, 50.0 mg / kg), detralex (75.0 mg / kg, per os) and levotetrasulfin forte (intraperitoneal, 0.1 ml / kg), the area of radiation ulcers in treated animals in the period from 98 to 126 days after irradiation was 26–80 % less compared to irradiated controls.
Conclusion: The experiments show the possibility of successful use of a complex antibiotic in combination with drugs that improve blood supply and trophism of irradiated tissues, in the treatment of severe local radiation lesions.
16-20
Features of Brain Damage after Gamma-Neutron Irradiation of the Head and Modification of the Damage by Lactoferrin
Abstract
Purpose: To investigate the effect of γ, n-irradiation of the mice head on the brain cells damage, behavior and cognition, and to examine the possibility of using lactoferrin (LF) to alleviate radiation-induced impairments.
Material and methods: Mice heads were irradiated in a beam of neutrons and gamma rays from the IR-8 nuclear reactor. The brain cells of control and irradiated mice were isolated using Percoll. Neurons and resting and activated microglia cells were analyzed using the fluorescently labeled antibodies and flow cytometry. The level of DNA double-strand breaks in neurons was determined by γH2AX histone content. Cytokine gene expression in the hippocampus was studied by RT-PCR. Behavior and cognitive functions were studied using the open field, Morris water maze and novel object recognition tests. LF was isolated from female colostrum by preparative ion-exchange chromatography and purified by affinity chromatography on heparin-sepharose.
Results: γ, n-Irradiation of the mice head at a dose of 1.5 Gy led to an increase in the level of DNA double-strand breaks in neurons. Twenty-four hours after irradiation the total number of cells and the number of neurons in the isolated fraction of brain cells decreased, but the number of microglial cells remained unchanged. The number of resting and activated microglia did not change within 3–72 h after γ, n-irradiation. The expression level of the TNFα, IL-1β, and IL-6 genes increased 2 months after γ, n-irradiation of the mice head at a dose of 1.5 Gy, indicating the development of neuroinflammation. At this time, irradiated mice demonstrated the anxiety-like behavior and impaired spatial and recognition memory. A single i.p. administration of human LF to mice immediately after γ, n-irradiation of the head did not affect the observed radiation-induced disturbances, but decreased the gene expression levels of TNFα, IL-1β and IL-6 pro-inflammatory cytokines and increased the gene expression level of TGFβ anti-inflammatory cytokine in the hippocampus 2 months after radiation exposure. The obtained results indicate a partial decrease in the level of hippocampal neuroinflammation of irradiated animals treated with LF.
Conclusion: γ, n-Irradiation of the mice head at a dose of 1.5 Gy leads to DNA damage of neurons and the decrease in the number of neurons. Microglia cells are more resistant to such radiation exposure. Late after head-only γ, n-irradiation, mice develop neuroinflammation, which is detected by an increase in the pro-inflammatory cytokine gene expression in the hippocampus and also by anxiety-like behavior and impaired cognitive functions. A single LF administration leads to a partial decrease in the neuroinflammation level, but does not affect the other studied parameters. The optimal dosing regimen of LF remains to be determined to preserve cognitive functions after γ, n-irradiation of the brain.
21-28
Radiation Medicine
System Criteria for Differential Express Diagnostics of Prenosological Disorders of Occupational Health of Employees at Nuclear Power Facilities
Abstract
Purpose: Development of complex criteria of differential express-diagnostics of pre-dosological disorders of occupational health of employees of nuclear facilities.
Material and methods: The study object was male workers of the main production facilities of the Electrohimpribor Combine undergoing periodic medical examinations and psychophysiological examinations. The state of health was assessed according to the employee’s belonging to the dispensary observation group in accordance with Order No. 404n of the Ministry of Health of the Russian Federation of April 27, 2021. The psychophysiological state was assessed using a hardware-software complex for group psychophysiological examination APK PFS-CONTROL. Additional testing techniques included assessment of vibraimage parameters, evaluated using computer programs HealthTest and VibraMI, developed in ELSIS (St. Petersburg). Totally 943 man-surveys were carried out with different combination of testing methods. The average age of the workers was (42.0 ± 1.7) years, total work experience was (23 ± 1.3) years, and work experience in the specialty was (13.0 ± 1.8) years.
Results: As a criteria of prenosological health disorders we used the characteristics of the worker’s adaptation to the factors of life activity. Adaptation disorders are evaluated according to three specific criteria: 1) assessment of the functional state of the cardiovascular system according to HRV data; 2) rapid assessment of the psychophysiological state according to vibraimage parameters; 3) assessment of personal and special abilities according to multiple intelligence assessment. For each of the criteria a “traffic light” of states and decisive rules of their formalized identification were developed. Characteristics of unfavorable states are given. Complex express-diagnostics of pre-dosological disorders of occupational health is carried out using integral index, which is a weighted sum of private “traffic light” indexes with a ball score. The formalized express-diagnostics of premalignant disorders is carried out using linear discriminant functions with an average recognition accuracy of 96.4 % or a probabilistic nomogram, which allows to graphically estimate the risk level of health disorders.
Conclusion: Improvement of medical-psychophysiological support of employees of nuclear facilities is connected with introduction of methods and criteria of differential express-diagnosis of prenosological disorders of health. The developed criteria of express-diagnostics of pre-dosological disorders of occupational health expand the existing methodological and criteria base of periodic medical examinations of nuclear industry workers, strengthen their preventive orientation with the purpose of timely application of medical, psychophysiological, organizational and other measures on preservation and maintenance of occupational health of personnel.
29-34
To the Question about Pharmacological Protection during Irradiation in Non-Infecting Doses: Maybe, Necessary? Communication 3. Review of the Experience of Studying and Prospects for the Use of Anti-Radiation Medicines
Abstract
Purpose: Review and systematization of data on the development of studies of drugs intended for protection against radiation in medium doses, assessment of the latest proposals and directions of pharmacological influence on radiation effects, incitement to discussion on the issue under consideration.
Results: An analysis of domestic and foreign literature for the period of the 70–90s of the twentieth century and the latest period in relation to the prevention of tissue reactions and long-term effects of low-dose low-power irradiation was carried out, classes (groups) and samples of pharmaceuticals used were considered.
Conclusions: 1. Very diverse previously proposed pharmaceuticals are still suitable, acting on various mechanisms of the genesis of the consequences of exposure to medium doses. 2. In recent years, substances (drugs) with receptor action, including genetically engineered products, as well as gene therapy agents, have been of primary interest, but they have been little studied as the means of choice due to their status as demonstration samples for use at medium doses. 3. Drugs of choice, made on the basis of many considerations over 30 years ago, until a replacement not be found.
35-52
The First Radioprotectors: For in vivo Experiments the Official Historical Milestone is Postponed by Six Years
Abstract
Historical essays in monographs, in reviews and in the introductions of experimental works on theme of the first studies of radioprotectors are considered. It was found that such studies began to be carried out only during the development and use of atomic weapons, but not during the previous order of 40 years of radiotherapy (with the exception of the effect of hypoxia as such, and not caused by drugs).
In most publications, the work of Patt H.M. et al., 1949 on the cysteine action (USA) is called as pioneer research, what is not quite right (it is only right for thiol compounds). A paper by Joseph Maisin (Belgium) in the journal ‘Acta Biologica Belgica’ which published only in 1941–1943 in the occupied Brussels, should be considered as a real milestone for animal experiments (Vol. III–IV. P. 117). In this study, referenced only in a single work (Bacq Z.M. et al., 1951), the radioprotective effect of p-aminobenzoic acid (PABA) was demonstrated in rodents. In the same year, the radioprotective effect of estrogens was shown in mice (Treadwelal A. DEG. et al., February 1943).
A brief summary of the stages of radioprotective agents study is presented, starting from 1942 (W.M. Dale et al.; protection of the enzyme in solution) and up to the 1954, when all the main classes of radioprotectors were discovered and the corresponding mechanisms of effects were proposed.
53-59
Features of the Clinical Course of Acute Radiation Sickness of Middle Gravity Due to Short-Term External Extremely Ununiform Gamma-Neutron Exposure and Local Radiation Injuries of the Lower Limb and the Right Arm of III and IV Severity
Abstract
Purpose: The purpose of the work is to assess acute radiation sickness of moderate severity from short-term external extremely uneven gamma-neutron irradiation and local radiation injuries of the lower extremities and right hand of III and IV severity.
Material and methods: Patient T., born in 1940, at the age of 25, began working from 1965 to 1968 as an apparatchik in plant No. 1 of department 20 at Production Association «Mayak» in contact with plutonium. On December 10, 1968, at 11:30 p.m., the accident occurred. The victim was at a distance of about 50 cm from the source, which was below and mostly to the right of him. The patient was exposed to short-term exposure to neutrons and gamma radiation. A few minutes later, numbness appeared in the right half of the trunk and extremities. Twenty-five minutes later, vomiting appeared, vomiting was repeated: 8 times before admission to the hospital, at the health center, after washing in the shower, in the hospital. Made gastric lavage, intravenous administration of pentacin, diphenhydramine, glucose, bloodletting (500 ml), twice transfused blood (250 ml each), polyglucin (500 ml), promedol, atropine. On examination, slight hyperemia of the right half of the face, injection of the sclera was noted. In the blood test, made for the first time after 2 and a half hours from the start of the events, there were 9000 leukocytes, lymphocytes – 15 %. On the morning of December 11, 1968, the patient complained of a burning sensation in the right half of his face; repeated vomiting. There were 7600 leukocytes at that time. The victim was offered to go to the 6th Clinical Hospital in Moscow (Sector No. 9 of the Institute of Biophysics), the patient agreed.
Examination results: A clinical description of acute radiation sickness of moderate severity from short-term external extremely uneven gamma-neutron irradiation and local radiation injuries of the lower extremities and right arm of III and IV severity is given. The features of the clinical picture of radiation sickness were entirely determined by the nature of the acting radiation factor and the position of the radiation source in relation to the victim and the associated topography of the lesion. Irradiation was directed from bottom to top and from right to left, hence the difference in exposure doses: on the right, the dose changed from bottom to top from more than 2500 rad (foot, lower leg, right hand) to less than 250–300 rad (in the head region), while in the middle – in the area from the iliac crest to the costal arch – the dose exceeded 500 rad on the left; from bottom to top, the drop occurred from a dose close to 2000 rad (foot and lower third of the lower leg) to 460 rad (in the anterior spine of the left ilium). The neutron nature of the acting radiation factor caused damage to surface tissues and visceral organs and bone marrow, the latter to a lesser extent due to the smaller contribution of the gamma factor to this accident.
Conclusion: The primary reaction and laboratory data of the first days of the disease indicated a severe lesion. However, the hematological syndrome was not severe. If it were not for the pain syndrome associated with an extremely severe local injury, the general condition of the patient would not have been so severe. Local trauma, which endangered the life of the patient, led him to a deep disability. Therefore, despite the average severity of the hematological syndrome, this form of acute radiation sickness was regarded as severe. The weakening of the hematological syndrome, apparently, was caused by the extreme severity of the local injury, which played the role of a hematopoiesis stimulator.
60-66
The State of the Genome during Intrauterine Irradiation
Abstract
The widespread use of sources of ionizing radiation for diagnostic and therapeutic purposes dictates the need to study the effect of intrauterine exposure on health. The search for literature sources was carried out using the MEDLINE databases in the PubMed, CyberLeninka, elibrary.ru search engine using the key words: intrauterine exposure, gene, genome, genomic instability, cytogenetics, mutations, chromosomal aberrations, gene expression. The review uses full-text literature sources in Russian and English. The literature search ended in November 2021. The paper presents a review of the literature on the state of the genome during intrauterine irradiation. The paper presents a review of the literature on the state of the genome during intrauterine irradiation. The results of a study of persons exposed to intrauterine exposure during the atomic bombing in Japan, during medical and diagnostic procedures, as well as data obtained in experimental studies on animals indicate that the main radiation-induced effects of intrauterine exposure were early death of the embryo/fetus, congenital malformations, growth and intellectual development retardation with a threshold of at least 100 mGy. Genetic disorders have been studied both in animal experiments and in individuals exposed to intrauterine exposure as a result of the bombing of Hiroshima and Nagasaki in Japan, the accident at the Chernobyl nuclear power plant, in the offspring of parents exposed to occupational exposure, as well as in medical and man-made exposure. It was shown that changes in the genome depended on the type, dose, irradiation power and the phase of intrauterine development. Most aberrations of a stable type were represented by deletions and translocations. Unstable aberrations were also detected: paired fragments, centromeric breaks, dicentrics, rings.
67-74
Radiation Epidemiology
Risk Factors for Esophageal Cancer in the Cohort of Nuclear Facility Workers
Abstract
Purpose: To assess the influence of non-radiation factors and occupational radiation exposure on the incidence risk of esophageal cancer in nuclear workers considering various histological types of the cancer.
Material and methods: The study was designed as a retrospective analysis that considered data on the cohort of workers employed at reactors, radiochemical and plutonium production facilities of the Mayak Production Association (PA) who had been hired during 1948–1982. The total number of workers included in the cohort was 21645. Using the EPICURE software, the relative risk (RR) and excess relative risk of the esophageal cancer incidence per unit of the accumulated gamma dose from external exposure (ERR/Gy) were estimated based on the Poisson regression.
Results: By 31.12.2018, 47 esophageal cancers were reported in members of the study cohort; the majority of these cancers were squamous cell carcinomas. The incidence risk of esophageal cancer was lower in females than in males and it increased with attained age. The increased risk of esophageal cancer (all cases) was associated with current smoking (RR=12.6, 95 % CI 4.21, 42.13), gastroesophageal reflux disease (GERD) (RR=3.96, 95 % CI 1.60, 8.48), excess body weight and obesity (RR=1.21, 95 % CI 1.13, 2.08). The significantly increased RR of squamous cell esophageal carcinoma was found in current smokers and workers had GERD. The significantly increased RR of esophageal adenocarcinoma was found in current and former smokers. The risk of esophageal cancer (all cases and squamous cell carcinomas) was higher in workers who abused alcohol but the RR estimates were not statistically significant. A significant linear association of the esophageal cancer risk with gamma dose from external exposure was found: ERR/Gy=1.28 (95 % CI 0.21, 4.11) for all cases and ERR/Gy=1.01 (95 % CI 0.01, 3.95) for squamous cell carcinoma; these estimates are the risks adjusted for sex, age, smoking, alcohol, GERD and body mass index. No effect of occupational radiation exposure on the esophageal adenocarcinoma risk was found.
Conclusion: This study confirmed obtained earlier data on the impact of occupational external gamma exposure on the risk of esophageal cancer in Mayak PA workers. The estimates of ERR/Gy of external gamma-ray exposure were updated having made adjustments for the most important non-radiation factors.
75-79
Newborn Children Health Status in Families of Male Nuclear Power Plants Personnel
Abstract
Purpose: To give a general description of personnel exposure doses and assess the health status of newborn children in families of male nuclear power plants personnel.
Material and methods: The work includes the results of studies of the reproductive health of male personnel of Smolensk, Kursk, Kalinin and Novovoronezh NPPs. The source of information on annual doses of occupational exposure of personnel was the data from the Federal Bank of individual exposure doses of personnel of organizations and the population in the territories served by the FMBA of Russia. The state of newborns was assessed by indicators of physical development and the frequency of birth of a child with pathology. Intrauterine growth retardation, congenital malformations, and other perinatal diseases were noted in the structure of pathological conditions. The source of medical data was information from the individual medical records “History of childbirth” and “History of the development of the newborn” for 2007–2018.
Results: The health status of newborn children born in 2007–2018 in the families of male personnel of the considered NPPs and in control groups did not differ significantly in terms of selected indicators characterizing the adaptive capabilities of newborn children to extrauterine life. The proportion of healthy children ranged from 60 to 73 % of their total number. In the structure of pathological conditions, perinatal conditions made the greatest contribution (from 10 to 17 %). The birth rate of children with congenital malformations did not exceed 34,0±8,9 per 1000 newborns and was significantly lower than the level adopted by the ICRP for calculating radiation risk (60 per 1000). There were no differences in the influence of the maternal factor (age and complications during pregnancy) on the development of the fetus and the health of newborns in the families of male staff and control groups.
According to calculations, the accumulated individual doses of occupational exposure of male personnel before conception of children did not exceed 30 mSv (on average) and for more than 95 % of the personnel – 100 mSv, which is lower than the exposure doses (above 100 mSv) when the negative consequences of exposure of men were reliably observed in the offspring in radiation-epidemiological studies.
Conclusion: No influence of occupational exposure on the health status of newborn children in families of male nuclear power plant personnel has been identified. At the same time, it is proposed to conduct monitoring observations of the state of reproductive health of a small group of male personnel of nuclear power plants, whose accumulated effective doses may exceed 100 mSv.
80-84
Dosimetric Characteristics of the Cohort of the Siberian Chemical Plant Personnel in the Period 1950-2010
Abstract
Purpose: To give a dosimetric characterization of the personnel of the Siberian Chemical Plant (SCP) subjected to prolonged technogenic occupational exposure to ionizing radiation (IR) in the period 1950–2010, as well as the cohort of the personnel of the SCP involved in working with uranium compounds.
Material and methods: SCP is one of the largest and oldest complexes of nuclear industry enterprises in the world, having experience in continuous dosimetric monitoring of personnel for more than 60 years. The database of the regional medical-dosimetric register of employees of the SCP (RMDR) contains information about all employees of the SCP for the entire history of the enterprise, including personal data of medical, dosimetric and professional nature of 65.350 employees of the SCP, of which more than 32.000 people were exposed to chronic technogenic occupational radiation in the range of low doses. The archive of the medical documentation of the Seversk Biophysical Research Center contains 55.569 medical histories of the employees of the SCP, 29.800 outpatient records and 11.953 autopsy protocols.
Results: Employees of the radiochemical, chemical-metallurgical, sublimate and separation industries of the SCP were subjected to combined (external and internal) irradiation, while the personnel of the reactor production were exposed exclusively to external irradiation. Auxiliary production workers were mainly exposed to non-radiation factors. Individual dosimetric control (IDC) of external exposure was carried out for all workers who were in the zone of exposure to external radiation sources. The average accumulated dose of external radiation for employees of the SCP was 28.3 mSv. IDC of internal irradiation was carried out for all workers employed at the production site, where the excess of the regulatory level of the concentration of radionuclides in the air of the working area was detected. The average value of the activity of radionuclides in the urine of SCP workers does not exceed 0.74 Bq. The life status has been clarified for 80.8 % of the employees of the SCP. About 3.500 employees of the agricultural complex have an IDC for internal irradiation from uranium based on the results of a biophysical examination. The life status is established for 75 % of employees of the uranium cohort.
Conclusion: For the first time, a dosimetric characteristic of a cohort of 65.350 workers of the SCP (21 % women) who started work in the period 1950–2010 was given. The cohort of the staff of the SCP is suitable for conducting epidemiological studies in order to establish the risks associated with the impact on the human body of technogenic occupational exposure to IR.
85-91
Discussions
Recommendations for Amendments to the NRB-99/2009 and to the OSPORB-99/2010
Abstract
Purpose: In Russia, the main regulatory documents on radiation safety are being adjusted: Radiation Safety Standards (NRB-99/2009) and Basic Sanitary Rules (OSPORB-99/2010). The purpose of the work is to remove and correct certain incorrect provisions of these documents.
Results: The disadvantages of NRB-99/2009 related to the values of the minimum significant activity and the minimum significant specific activity of radionuclides were identified and justified.
In OSPORB-99/2010, the inadmissibility of introducing minimally licensed activity of radionuclides in closed sources of ionizing radiation into Sanitary Rules was identified and justified. An unacceptably large amount of this activity can lead to overexposure of personnel and the public in incidents with these sources.
Conclusions: The following recommendations were made for the adjustment of NRB-99/2009 and OSPORB-99-2010:
– in NRB-99/2009, it is recommended to completely remove the minimally significant specific activities, and use the minimally significant activities in accordance with NRB-76/87.
– in OSPORB-99/2010, it is recommended to remove all provisions related to the minimum licensed activity of radionuclides in closed sources of ionizing radiation.
Key words: radiation safety, regulatory documents, minimally significant activity, minimally significant specific activity, closed sources of ionizing radiation
92-94
To the Discussion on Amendments to NRB-99/2009 and to OSPORB-99/2010
95-98
Anniversary
Leonid Andreevich Ilyin (on the Occasion of His 95th Birthday)
Abstract
Full member of the Russian Academy of Sciences, Doctor of Medical Sciences, Professor Leonid Andreevich Ilyin is a recognized world authority in the field of radiation medicine, biomedical and hygienic aspects of radiation protection. From 1968 to 2008 for 40 years – director and scientific director of the State Scientific Center of the Order of Lenin of the Institute of Biophysics. Since 2008 – Honorary President of the Federal State Budgetary Institution «State Research Center of the Russian Federation – A.I. Burnazyan Federal Medical Biophysical Center» (after the merger of the Institute of Biophysics and Clinical Hospital No. 6).
Thanks to the work of Academician Ilyin, his students and colleagues, highly effective drugs for the prevention and treatment of acute radiation injuries were created, tested and entered into domestic practice. Repeatedly took part as a supervisor in testing the developed drugs in field conditions. He is a veteran of special risk units. L.A. Ilyin is the first scientist in the world who developed and substantiated the forecast of the radiological consequences of the Chernobyl disaster, subsequently confirmed by leading foreign and domestic experts.
99-104