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Russian Journal of Occupational Health and Industrial Ecology

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No 9 (2024)
https://doi.org/10.31089/1026-9428-2024-64-9

ORIGINAL ARTICLES

566-574 181
Abstract

Introduction. Osimertinib, a 3rd generation epidermal growth factor receptor tyrosine kinase inhibitor, is currently the only drug registered for the treatment of metastatic non-small cell lung cancer in patients with a positive T790M mutation status. The production of osimertinib mesylate is planned on the territory of the Russian Federation, which necessitates research to substantiate the hygienic standard for the aerosol content of the substance in the air of the working area. Conducting research to substantiate the maximum permissible concentration of a substance requires significant material and time resources, while using the results of preclinical and clinical studies, mathematical modeling of processes, and risk assessment methodology allows for a comprehensive assessment of the substance, while significantly reducing the time and cost of work.

The study aims to scientifically substantiate the maximum permissible concentration of the pharmaceutical substance osimertinib mesylate in the air of the working area using data from toxicological studies and mathematical modeling of the effects of the substance on humans in industrial conditions.

Materials and methods. The materials used were domestic and international databases, reports, research protocols, scientific articles and monographs containing information on the physico-chemical and toxic properties, pharmacotherapeutic activity of osimertinib.

Results. The specialists have conducted hygienic regulation of osimertinib, taking into account data on its toxicity, danger, pharmacotherapeutic activity, side effects, long-term consequences, pharmacokinetic studies and modeling. To substantiate the value of the maximum permissible concentration, the authors used the reference points: an inactive NOEL level of 1 mg/­kg/­day for general toxic effect, established in a 92-day experiment on rats with intragastric administration; the lowest observed level of adverse effects of LOAEL is 0.5 mg/kg/day for general toxic effect, established in a 180-day experiment on dogs with intragastric administration; the level that does not cause adverse effects of NOAEL is 10 mg/kg/day for general toxic effect, established in a 180-day experiment on mice with intragastric administration. Safe concentrations of osimertinib in the air of the work area were evaluated using reference points, including the pharmacological effect and the minimum daily therapeutic dose; toxicokinetic modeling of concentrations of a substance in the human body under production conditions and the level of minimal risk.

Limitation. The study is limited to the review of open literature sources describing the toxicological/toxicokinetic characteristics of osimertinib mesylate.

Conclusion. The most stringent indicators of safe exposure levels, established on the basis of pharmacological effect and toxicokinetic modeling in dogs, allowed us to recommend 0.005 mg/m3, aerosol, hazard class 1 as the maximum permissible concentration in the air of the working area for osimertinib mesylate.

Ethics. This study did not require the conclusion of the Ethics Committee.

Contribution:
Khamidulina Kh.Kh. — the concept and design of the study, writing the text, the editing;
Ukolov A.I. — data collection and processing, writing the text;
Radilov A.S. — the concept and design of the study, the editing;
Tarasova E.V. — the concept and design of the study, data collection and processing, writing the text;
Zamkova I.V. — data collection and processing, writing the text.

Gratitude. The authors are grateful to Mrs. Alla Yu. Savchenko, Cand. of Sci. (Med.), Associate Professor of the Department of Industrial Pharmacy of the Scientific Research Nuclear University.

Funding. The study had no funding.

Conflict of interests. The authors declare no conflict of interests.

Received: 17.09.2024 / Accepted: 24.09.2024 / Published: 10.10.2024

575-581 154
Abstract

Introduction. Electric and magnetic fields of industrial frequency are an integral part of production processes, and their effect on the human body is of increasing interest both among scientists and among specialists in the field of medicine and occupational safety. In recent decades, there has been growing concern about the potential impact of these areas on the health of workers, especially those who are exposed to prolonged exposure in the course of their professional activities. In this context, we pay special attention to the neuroendocrine system, which plays a key role in regulating many physiological processes, including metabolism, stress reactions and maintaining homeostasis. The study of the fundamentals of the neuroendocrine system and the mechanisms of the effect of electromagnetic fields on the body not only contributes to the deepening of scientific knowledge in the field of biomedical research, but also has practical significance in ensuring occupational safety and improving working conditions in industrial enterprises, allowing to identify possible health consequences and develop effective measures to protect workers from negative bioeffects.

The study aims to research the effects of electric and magnetic fields of industrial frequency on the functional state of the hypothalamic-pituitary-adrenal system of employees of electric grid facilities.

Materials and methods. Specialists examined 144 employees of the main group engaged in the repair and operation of electric grid facilities and 40 employees of the control group who were not exposed to electromagnetic fields of industrial frequency. We determined the concentration of adrenocorticotropic hormone, cortisol and dehydroepiandrosterone sulfate in blood serum samples and calculated the ratio of dehydroepiandrosterone sulfate to cortisol.

Results. Workers exposed to the combined effects of electric and magnetic fields of industrial frequency had a lower (p<0.05) level of adrenocorticotropic hormone (1.9 [0.5; 3.9] pg/ml) and dehydroepiandrosterone sulfate (5.8 [3.7; 8.4] mmol/l) in the blood compared with the group of workers exposed to magnetic fields industrial frequency fields (4.4 [2.1; 12.9] pg/ml; 9.8 [6.3; 14.5] mmol/l) and to the control group (6.4 [4.0; 19.8] pg/ml; 7.8 [4.7; 13.3] mmol/l), respectively. The scientists also revealed in the group of workers exposed to combined exposure in the field, the association of a low ratio of dehydroepiandrosterone sulfate and cortisol with the development of cardiovascular diseases and feedback from work experience (p<0.05).

Limitations. The study is limited by the number of people surveyed (144 employees).

Conclusion. The results of the study indicate the hypoactivity of the hypothalamic-pituitary-adrenal system induced by exposure to electric and magnetic fields of industrial frequency, manifested by a decrease in the level of adrenocorticotropic hormone, dehydroepiandrosterone sulfate and its relationship to cortisol in workers exposed to combined effects of electric and magnetic fields of industrial frequency.

Ethics. The work complies with ethical standards developed in accordance with the Helsinki Declaration of the World Medical Association «Ethical Principles of conducting Scientific medical research with human participation» as amended in 2000 and the «Rules of Clinical Practice in the Russian Federation» approved by Order of the Ministry of Health of the Russian Federation dated 04/01/2016 No. 200n. We received informed consent from each examined person to participate in the study, approved in accordance with the established procedure by the local Ethics Committee of Izmerov Research Institute of Occupational Health (minutes of the meeting of the Ethics Committee No. 17 dated 12/16/2015).

Contribution:
Kuzmina L.P. — concept and design of the study, editing;
Kislyakova A.A. — research concept and design, data collection and processing, text writing, editing;
Anokhin N.N. — research concept and design, writing, editing.

Funding. The study had no funding.

Conflict of interests. The authors declare no conflict of interests.

Received: 19.09.2024 / Accepted: 27.09.2024 / Published: 10.10.2024

582-587 99
Abstract

Introduction. Experts do not take into account the presence of subclinical atherosclerosis when stratifying risk on the SCORE scale, however, it is the main substrate for the occurrence of cardiovascular disasters. Most primary cardiovascular events occur in low cardiovascular risk groups, which requires timely detection of atherosclerosis and preventive measures to preserve the working population’s ability to work and reduce the economic burden of treatment of cardiovascular diseases.

The study aims to research the incidence of atherosclerosis in workers of the main professions of the coal industry in the South of Kuzbass in groups of medium and high risk of fatal events on the SCORE scale.

Materials and methods. We divided the subjects into two groups using the SCORE scale: high-risk (main) — from 5 to 9%, which included 60 people, and moderate-risk group — from 2 to 4% (comparison) — 70 employees. The average age of the first was 50.98±0.43 years, the comparison group was 49.96±0.35 years (p=0.070). The scientists examined the indicators of blood pressure, lipid, carbohydrate and purine metabolism, and performed an ultrasound examination of the main arteries.

Results. The incidence of atherosclerotic plaques in at least one vascular basin was 80.0% in the main group and 78.6% in the comparison group, p=0.845. The frequency of carotid artery atheromas in the high-risk group on the SCORE scale (52.7%) did not significantly differ from the comparison group (54.3%), p=0.862; a similar pattern in the arteries of the lower extremities: 80.0% vs. 70.0%, respectively, p=0.203. The frequency of carotid artery atheromas in the high-risk group on the SCORE scale (52.7%) did not significantly differ from the comparison group (54.3%), p=0.862; a similar pattern in the arteries of the lower extremities: 80.0% vs. 70.0%, respectively, p=0.203. The combination of thickening of the intima of vessels and the presence of atheromas tended to be more frequent in the main group — 83.6% compared with those in the comparison group — 70.1%, p=0.076

Limitations. The study is limited by the number of examined patients who underwent periodic medical examination at the Scientific Research Institute of Complex Problems of Hygiene and Occupational Diseases.

Conclusion. The incidence of atherosclerosis among employees of coal enterprises turned out to be very high and did not statistically differ in the groups of medium and high fatal risk stratified on the SCORE scale, which requires more thorough screening and measures of enhanced angioprotective prevention, even in people with a low risk of fatal cardiovascular disasters.

Ethics. All the subjects signed an informed consent to participate in the study, the Protocol of which corresponded to the requirements of the Bioethical Committee of the Research Institute of Complex Problems of Hygiene and Occupational Diseases, executed in accordance with the Helsinki Declaration of the World Medical Association «Ethical Principles of conducting medical research with human participation as a subject» as amended in 2013 and the «Rules of Good Clinical Practice» approved by the order Ministry of Health of the Russian Federation No. 200n dated April 1, 2016.

Contribution:
Filimonov E.S. — research concept and design, statistical processing, text writing;
Korotenko O.Yu. — collecting material, writing text;
Ulanova E.V. — collection of material.

Funding. The study had no funding.

Conflict of interests. The authors declare no conflict of interests.

Received: 21.06.2024 / Accepted: 15.08.2024 / Published: 10.10.2024

588-594 90
Abstract

Introduction. The significant prevalence of anthracosilicosis and silicosis, characterized by the rapid development of pneumofibrosis in coal mine workers, is a serious socially significant problem worldwide. A key component of the pathogenesis of pneumoconiosis is the macrophage reaction to fibrogenic dust, which is a complex immunological response, with prolonged and intense exposure leading to chronic inflammation in various organs and systems, fibrosis and a progressive decrease in their functions. A deep understanding and evaluation of the macrophage reaction as a potential biomarker for the diagnosis of lung damage in miners will allow us to develop more effective strategies to combat dust damage to organs and systems.

The study aims to consider macrophage hyperfunction as a trigger mechanism for fibroplastic changes in internal organs in pneumoconiosis in miners.

Materials and methods. Using light microscopy, specialists conducted extended cytological, histological and immunohistochemical studies of bronchial smears and autopsy material (fragments of bronchi, lungs, heart, liver and kidneys) of 50 miners of Kuzbass coal enterprises who died simultaneously as a result of a man-made disaster. Morphometric analysis of histological structures with measurement of linear dimensions was used for a comprehensive assessment of pathomorphological changes.

Results. There was a sharp increase in the number and size of actively phagocytic alveolar macrophages loaded with dust particles in the lungs of miners. Pathological changes in internal organs were characterized by pronounced fibrosis in the peribronchial and perivascular zones, stroma with deposition of dust particles and a pronounced macrophage reaction. In a group of miners with more than 15 years of experience in the central and distal parts of the lungs, in the intermuscular zones of the myocardium, the portal tracts of the liver, and the central segments of the kidneys, there was a constant increase in the expression of immunohistochemical markers CD14, CD34, actin and vimentin, which can be used as diagnostic markers for the identification of macrophage inflammation and fibrosis, will allow to assess the degree of severity of the pathological process. A characteristic feature of the miners' long experience of dust exposure was the presence of progressive pronounced perivascular sclerosis extending beyond the vascular histione. Experts found fibroblastic cells with positive expression of CD14, CD31 and CD34 in the sclerotic zones.

Limitation. The absence of cytogenetic and electron microscopic examination, which is expected in the future in conjunction with the expansion of the range of immunohistochemical research methods.

Conclusion. The results of extended pathomorphological and cytological studies emphasize the importance of an integrated approach to the diagnosis of occupational diseases in the coal industry. The use of a combination of these methods will allow timely detection of macrophage inflammation and fibrous process in dust pathology, specific changes at the cellular and tissue levels, as well as to assess the severity of the pathological process.

Ethics. The study of autopsy material was based on a secondary examination of blocks and ready-made histological micro-preparations (glasses) of the material of the Bureau of Forensic Medical examination of Novokuznetsk, Osinniki, Prokopyevsk. The studies of pathomorphological material were carried out strictly on the basis of Federal Law No. 323-FZ dated 11/21/2011 "On the Basics of Protecting the Health of Citizens in the Russian Federation", in particular Article 67 "Conducting pathological anatomical autopsies", Federal Law No. 8-FZ dated 12.01.1996 "On Burial and Funeral Business" (Article 5, pp. 1, 2), as well as in accordance with the Order of the Ministry of Health of the Russian Federation dated 06.06.2013 No. 354n "On the procedure for conducting pathological anatomical autopsies", Order of the Ministry of Health of the Russian Federation dated 03/24/2016 No. 179n "On the Rules for conducting pathological anatomical studies".

Contribution:
Bondarev O.I. — the concept and design of the study, data collection and processing, writing the text;
Bugaeva M.S. — data collection and processing, the editing;
Ulanova E.V. — collection and analysis of literature;
Kizichenko N.V. — collection and analysis of literature.

Funding. The study had no funding.

Conflict of interests. The authors declare no conflict of interests.

Received: 30.05.2024 / Accepted: 19.09.2024 / Published: 10.10.2024

595-602 134
Abstract

Introduction. Aluminum production is accompanied by emissions of pollutants that can negatively affect the environment and public health.

The study aims to determine the impact of atmospheric emissions from an aluminum plant on the health of the population of the city of Novokuznetsk based on a risk assessment.

Materials and methods. The volume of maximum permissible emissions of the Novokuznetsk Aluminum Plant was used in the work. Experts calculated the maximum and average concentrations of substances at 40 exposure points. The maximum permissible concentrations of substances were determined in accordance with SanPiN 1.2.3685-21. The authors calculated the carcinogenic risk and the risk of non-carcinogenic effects in accordance with the Guidelines 2.1.10.1920-04. They carried out the classification of risk levels based on methodological recommendations 2.1.10.0156-19. 2.1.10.

Results. The authors have selected pollutants were for risk assessment: inorganic dust with a SiO2 content of <20%, sulfur dioxide, benz(a)pyrene, hydrogen fluoride, carbon monoxide, nitrogen dioxide, suspended solids, nitrogen oxide, carbon (soot). The maximum concentrations were 0.1–3.77 MPC for inorganic dust (SiO2<20%), 0.1–2.64 MPC for hydrogen fluoride and 0.05–1.74 MPC for sulfur dioxide; average concentrations were up to 9.16 MPC for benz(a)pyrene. The hazard indices for acute exposure are at an acceptable level; For chronic exposures, they correspond to alarming and high levels, reaching the highest value (13.469) at a point located closer to the sources of emissions. Hazard indices for critical organs and systems in acute exposures are at acceptable or minimum (target) levels, in chronic exposures they correspond to alarming and high-risk levels. The respiratory and immune systems are most affected. The total individual carcinogenic risk ranges from 4×10–7 to 8×10–6, without exceeding the upper limit of the permissible risk. Residents of the Kuznetsk district of the city are most affected by emissions.

Limitations. The main limitation in the work carried out was the use of calculated concentrations of pollutants for risk assessment without the use of in-kind indicators.

Conclusion. Elevated concentrations of pollutants were detected in the atmospheric air of residential areas adjacent to the territory of the aluminum plant, which determine alarming and high levels of non-carcinogenic risk to public health.

Ethics. This study did not require the conclusion of the Ethics Committee.

Contribution:
Surzhikov D.V. — the concept and design of the study, the editing;
Kislitsyna V.V. — the concept and design of the study, writing the text, the editing;
Golikov R.A. — data collection and processing;
Likontseva Yu.S. — data collection and processing, writing the text;
Steiger V.A. — data collection and processing.

Funding. The study had no funding.

Conflict of interests. The authors declare no conflict of interests.

Received: 13.09.2024 / Accepted: 18.09.2024 / Published: 10.10.2024

603-609 103
Abstract

Introduction. During operation, machine-building enterprises emit pollutants that can negatively affect the health of the population.

The study aims to determine the impact of emissions from a machine–building plant, as well as background atmospheric pollution, on the health risk of the population of Novokuznetsk.

Materials and methods. The work used data from the volume of maximum permissible emissions of a machine-building plant. The researchers calculated the maximum and average concentrations of pollutants using the "ECOcenter – Standard" program at 36 exposure points selected on the city map. Experts determined the maximum permissible concentrations of pollutants in the atmosphere in accordance with SanPiN 1.2.3685-21. The authors calculated the risks to public health in accordance with the Guidelines R 2.1.10.1920-04. The classification of risk levels was carried out on the basis of MP 2.1.10.0156-19. 2.1.10. Scientists also made a risk assessment considering background atmospheric pollution.

Results. Specialists carried out a risk assessment from exposure to nitrogen dioxide, carbon monoxide, sulfur dioxide, carbon (soot), inorganic dust, hexavalent chromium. The maximum and average concentrations of pollutants, as well as the maximum concentrations calculated taking into account background pollution, did not exceed the maximum permissible level. The average concentrations of nitrogen dioxide and hexavalent chromium, taking into account the background, exceeded the hygienic standard. The values of the hazard indices for acute and chronic exposures without taking into account the background, as well as for acute exposures taking into account the background, corresponded to the minimum (target) risk level. The values of the hazard indices for chronic inhalation effects, considering the background, corresponded to the alarming risk level at five points, amounting to 3.084–3.800. With chronic exposure, taking into account the background, an alarming level of risk was revealed for the effect on the respiratory organs (at four points the hazard index was 3.117 to 3.616) and blood (at three points the hazard index was in the range from 3.090 to 3.433). The total individual carcinogenic risk, excluding background, did not exceed the permissible level, ranging from 1.08×10–8 to 2.43×10–7 at different points, taking into account the background, amounted to 1.79×10–4–2.26×10–4, which corresponds to an alarming level. Hexavalent chromium makes the main contribution to the formation of carcinogenic risk.

Limitations. Calculated concentrations of pollutants were used to assess the risks.

Conclusion. The risks from exposure to atmospheric emissions from the machine-building plant correspond to the minimum (target) level. Background concentrations of toxic substances in chronic inhalation exposures determine an alarming level of non-carcinogenic risk at five points, as well as an alarming level of carcinogenic risk at all points of exposure.

Ethics. This study did not require the conclusion of the Ethics Committee.

Contribution:
Kislitsyna V.V. — the concept and design of the study, writing the text, editing;
Surzhikov D.V. — the concept and design of the study, editing;
Golikov R.A. — data collection and processing;
Likontseva Y.S. — data collection and processing, writing the text;
Motuz I.Y. — data collection and processing;

Funding. The study had no funding.

Conflict of interests. The authors declare no conflict of interest.

Received: 21.05.2024 / Accepted: 04.07.2024 / Published: 10.10.2024

DISCUSSIONS

610-620 158
Abstract

Hygienic rationing is an integral part of national measures in the field of occupational safety and health of workers. The current norms of general industrial vibration, as is known, are not safe. This determines the urgency of improving the system of hygienic rationing of general vibration, which, despite the achievements of science and technology, the emergence of a new controlled vibration parameter — full vibration acceleration, the introduction of a risk-based approach to rationing, has remained virtually unchanged for almost four decades.

The study aims to analyze domestic and international approaches to the assessment and normalization of general industrial vibration to justify the transition to a risk-oriented single-digit regulation of full vibration acceleration.

The authors carried out an expert and analytical study, analyzed and compared the materials of domestic and foreign regulations, methodological documents and literary sources on various aspects of the problem of rationing general industrial vibration.

Scientists have developed a new system for rationing the unfavorable factor of the production environment — general vibration, which establishes an integral standard for complete vibration acceleration, instead of differentiated rationing by vibration sources (transport, transport-technological, man-made) and directions of vibration action along the axes of the basocentric coordinate system (Z, X, Y). The new standard for full vibration acceleration is harmonized with ISO 2631 standard, Directive 2002/44/EC, standards adopted in foreign countries, and, according to calculations, can be approximately 0.56 m/s2 or 115 dB, which requires experimental studies to verify.

The new risk-oriented system of rationing of the industrial general vibration will make it possible to objectify the assessment of workers’ working conditions and, as a result, streamline and update the examination of the connection of the disease with the profession.

Contribution:
Prokopenko L.V. — concept and design of research, analysis of normative acts and literary sources, writing and editing of text;
Kuryerov N.N. — research design, analysis of normative acts and literary sources, writing the text;
Lagutina A.V. — research design, analysis of normative acts and literary sources, writing, editing.

Funding. The study had no funding.

Conflict of interests. The authors declare no conflict of interests.

Received: 12.09.2024 / Accepted: 20.09.2024 / Published: 10.10.2024

FOR THE PRACTICAL MEDICINE

621-627 145
Abstract

According to leading experts of the World Health Organization, the threat of a new strain of SARS-CoV-2 coronavirus remains, which will lead to a sharp increase in morbidity and mortality. The severity of complications after COVID-19 depends not only on how severe the disease was, but also on other factors: genetic predisposition, age, concomitant diseases, and working conditions. This makes it urgent to conduct further scientific research on the ranking of the factors of the production environment that accelerate the spread of COVID-19.

The study aims to determine the degree of occupational risk, taking into account the timing and frequency of manifestations of post-COVID syndrome (U09.9; U10.9 according to ICD–X) in specialists with intensive computer workload.

In the period 2020–2024, the researchers conducted a survey at the workplaces of Kislovodsk enterprises and examined 556 people with an intensive computer load associated with servicing the flows of mass consumers during the pandemic and in the post-pandemic period. We have studied the timing and frequency of the occurrence of post-COVID syndrome, objectified by the degree of health risk factors in various categories of workers with intensive computer workload.

The timing and frequency of seven post-COVID syndrome manifestations ranked (according to the degree of occupational health risk factors) (U09.9; U10.9 according to ICD-X) that occur in workers with intensive computer workload in the first two weeks after discharge from the hospital during hospitalization for COVID-19 (occupational health risk factors category A) or arising within three to four weeks after discharge from the hospital during hospitalization for COVID-19 (occupational health risk factors of category B).

Based on statistical and clinical and hygienic data obtained in the period from 2020 to 2024, post-COVID manifestations in the gradations of «high» and «moderately high» occupational health risk for employees (n=556) with intensive computer load were ranked by the timing and frequency of occurrence of the named syndrome, as well as by the degree of risk of potential COVID-19 infections of the named groups of specialists associated with servicing mass consumer flows infected with constantly mutating representatives of enveloped RNA viruses. According to the degree of occupational risk to the health of persons with intensive computer workload, six groups of specialists associated with servicing mass consumer flows, potentially infected with COVID-19 and other representatives of enveloped RNA viruses, were ranked.

Limitations. Post-COVID syndromes that occur within one to two and three to four weeks after discharge from the hospital have been studied.

Ethics. Scientists have conducted research in accordance with the principles of biomedical ethics and approved by the local Ethics Committee of Izmerov Research Institute of Occupation Health, Moscow (Protocol No. 4 dated 04/14/2021). Each participant of the study submitted a voluntary written informed consent signed by him after explaining to him the potential risks and benefits.

Contribution:
Golovkova N.P. — concept, editing; approval of the final version of the article;
Kuzmina L.P. — concept, editing; approval of the final version of the article;
Afanasyeva Yu.F. — collection of material, data processing, compilation of tables and graphs;
Bezrukavnikova L.M. — collection of literature data, editing.

Funding. The study had no funding.

Conflict of interests. The authors declare no conflict of interests.

Received: 05.06.2024 / Accepted: 29.09.2024 / Published: 10.10.2024

BRIEF REPORTS

628-632 149
Abstract

Working conditions at lead production plants, where a large number of harmful chemicals are present in the air of the work area, among which lead is the leading risk factor, have a negative impact on the health of workers. This xenobiotic disrupts numerous biochemical processes and affects many body systems. Of particular interest is the understanding of the action of lead at the molecular level, since in addition to the general mechanisms of damage to molecules and ultrastructures as a result of oxidative stress, lead is able to bind to a large DNA groove. A change in the level of gene expression in response to toxic exposure is considered as one of the biomarkers of the effect and can serve to develop measures for the early diagnosis of health disorders in exposed populations, including those working in harmful conditions.

The study aims to consider the expression of DNA repair genes in workers of lead processing from secondary raw materials.

The researchers examined the interned men working at the enterprise for the production of lead from secondary raw materials in the profession of a smelter (n=11) of the rough lead department, a dryer (n=10) of the rough lead department.

The comparison group included men (n=20) who work at the same enterprise and have no contact with harmful factors of production. We have performed amplification of the studied genes (ATM, CDKN1A and MDM) in real time using the QuantStudio 3 amplifier (Thermo Fisher Scientific, USA).

It was found that the expression level of the ATM gene was statistically significantly different in all three study groups from the comparison group. The expression of the CDKN1A gene increased in comparison with the comparison group only in the smelters of the refining department. Also, the expression of this gene was increased in the smelters of the refining department compared with the smelters of the rough lead department.

In this study, an increase in the expression level of CDKN1A in smelters of the refining department was demonstrated, which may be an adaptive mechanism of the repair system. Also, in all exposed groups, the researchers found a decrease in the expression level of the ATM gene, which is important for maintaining cellular homeostasis. Further studies of the mechanisms of the influence of lead on the expression of these two genes in experimental models will allow the use of expression levels as early biomarkers of the effect of both total Pb exposure (ATM gene) and dose-dependent (CDKN1A gene).

Limitations. Ethnicity was not determined in this study.

Ethics. The studies were conducted in accordance with the ethical principles set out in the Helsinki Declaration of the World Medical Association and approved by the local Ethics committee of the Federal State Budgetary Institution of the Russian National Research Center of Rospotrebnadzor (Protocol No. 1 of 02/26/2021).

Contribution:
Shaikhova D.R. — the concept and design of the study, the collection of material and data processing, the writing of the text;
Kikot A.M. — research concept and design, material collection and data processing, text writing;
Bereza I.A. — concept and design of research, collection of material and data processing, writing text;
Sutunkova M.P. — concept and design of the study, editing;
Bragina I.V. — concept and design of the study, editing;
Gurvich V.B. — concept and design of the study, editing.

Funding. The study had no funding.

Conflict of interests. The authors declare no conflict of interests.

Received: 20.08.2024 / Accepted: 12.09.2024 / Published: 10.10.2024



ISSN 1026-9428 (Print)
ISSN 2618-8945 (Online)