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<article article-type="research-article" dtd-version="1.3" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xml:lang="ru"><front><journal-meta><journal-id journal-id-type="publisher-id">medlit</journal-id><journal-title-group><journal-title xml:lang="ru">Гигиена и санитария</journal-title><trans-title-group xml:lang="en"><trans-title>Hygiene and Sanitation</trans-title></trans-title-group></journal-title-group><issn pub-type="ppub">0016-9900</issn><issn pub-type="epub">2412-0650</issn><publisher><publisher-name>Federal Scientific Center of Hygiene named after F.F. Erisman</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.47470/0016-9900-2023-102-11-1215-1223</article-id><article-id custom-type="edn" pub-id-type="custom">pndvie</article-id><article-id custom-type="elpub" pub-id-type="custom">medlit-3532</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="ru"><subject>ПРОФИЛАКТИЧЕСКАЯ ТОКСИКОЛОГИЯ И ГИГИЕНИЧЕСКОЕ НОРМИРОВАНИЕ</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="en"><subject>PREVENTIVE TOXICOLOGY AND HYGIENIC STANDARTIZATION</subject></subj-group></article-categories><title-group><article-title>Апоптоз как механизм гибели клеток дыхательной системы человека при воздействии углеродных нанотрубок</article-title><trans-title-group xml:lang="en"><trans-title>Apoptosis as a mechanism of human respiratory cell death upon exposure to carbon nanotubes</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0001-9506-563X</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Фатхутдинова</surname><given-names>Лилия Минвагизовна</given-names></name><name name-style="western" xml:lang="en"><surname>Fatkhutdinova</surname><given-names>Liliya M.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Д.м.н., заведующий кафедрой гигиены, медицины труда, ФГБОУ ВО Казанский ГМУ Минздрава России, 420012, Казань, Россия</p><p>e-mail: liliya.fatkhutdinova@kazangmu.ru</p></bio><bio xml:lang="en"><p>MD, PhD, DSci., Head of the Department of Hygiene and Occupational Medicine, Kazan State Medical University, Kazan, 420012, Russian Federation.</p><p>e-mail: liliya.fatkhutdinova@kazangmu.ru</p></bio><email xlink:type="simple">liliya.fatkhutdinova@kazangmu.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0003-2616-5017</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Габидинова</surname><given-names>Гульназ Фаезовна</given-names></name><name name-style="western" xml:lang="en"><surname>Gabidinova</surname><given-names>Gulnaz F.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Ассистент кафедры гигиены, медицины труда ФГБОУ ВО Казанский ГМУ Минздрава России, 420012, Казань, Россия</p><p>e-mail:  gulnaz.gabidinova@kazangmu.ru</p></bio><email xlink:type="simple">gulnaz.gabidinova@kazangmu.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0001-7497-1211</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Димиев</surname><given-names>Айрат Маратович</given-names></name><name name-style="western" xml:lang="en"><surname>Dimiev</surname><given-names>Аirat М.</given-names></name></name-alternatives><bio xml:lang="ru"><p>К.х.н, ведущий научный сотрудник ФГАОУ ВО «Казанский (Приволжский) федеральный университет», 420008, Казань, Россия</p></bio><email xlink:type="simple">noemail@neicon.ru</email><xref ref-type="aff" rid="aff-2"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0001-7080-3878</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Валеева</surname><given-names>Елена Валерьевна</given-names></name><name name-style="western" xml:lang="en"><surname>Valeeva</surname><given-names>Elena V.</given-names></name></name-alternatives><bio xml:lang="ru"><p>К.б.н., старший научный сотрудник Центральной научно-исследовательской лаборатории ФГБОУ ВО Казанский ГМУ Минздрава России, 420012, Казань, Россия</p><p>e-mail: elena.valeeva@kazangmu.ru</p></bio><email xlink:type="simple">elena.valeeva@kazangmu.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-2479-2474</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Тимербулатова</surname><given-names>Гюзель Абдулхалимовна</given-names></name><name name-style="western" xml:lang="en"><surname>Timerbulatova</surname><given-names>Gyuzel A.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Старший преподаватель кафедры гигиены, медицины труда ФГБОУ ВО Казанский ГМУ Минздрава России, 420012, Казань, Россия</p><p>e-mail: guzel.timerbulatova@kazangmu.ru</p></bio><email xlink:type="simple">guzel.timerbulatova@kazangmu.ru</email><xref ref-type="aff" rid="aff-1"/></contrib></contrib-group><aff-alternatives id="aff-1"><aff xml:lang="ru"><institution>ФГБОУ ВО «Казанский государственный медицинский университет» Министерства здравоохранения Российской Федерации</institution><country>Россия</country></aff><aff xml:lang="en"><institution>Kazan State Medical University</institution><country>Russian Federation</country></aff></aff-alternatives><aff-alternatives id="aff-2"><aff xml:lang="ru"><institution>ФГАОУ ВО «Казанский (Приволжский) федеральный университет»</institution><country>Россия</country></aff><aff xml:lang="en"><institution>Kazan Federal University</institution><country>Russian Federation</country></aff></aff-alternatives><pub-date pub-type="collection"><year>2023</year></pub-date><pub-date pub-type="epub"><day>13</day><month>12</month><year>2023</year></pub-date><volume>102</volume><issue>11</issue><fpage>1215</fpage><lpage>1223</lpage><permissions><copyright-statement>Copyright &amp;#x00A9; Фатхутдинова Л.М., Габидинова Г.Ф., Димиев А.М., Валеева Е.В., Тимербулатова Г.А., 2023</copyright-statement><copyright-year>2023</copyright-year><copyright-holder xml:lang="ru">Фатхутдинова Л.М., Габидинова Г.Ф., Димиев А.М., Валеева Е.В., Тимербулатова Г.А.</copyright-holder><copyright-holder xml:lang="en">Fatkhutdinova L.M., Gabidinova G.F., Dimiev А.М., Valeeva E.V., Timerbulatova G.A.</copyright-holder><license xml:lang="ru" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>Данная работа распространяется под лицензией Creative Commons Attribution 4.0.</license-p></license><license xml:lang="en" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>This work is licensed under a Creative Commons Attribution 4.0 License.</license-p></license></permissions><self-uri xlink:href="https://www.rjhas.ru/jour/article/view/3532">https://www.rjhas.ru/jour/article/view/3532</self-uri><abstract><sec><title>Введение</title><p>Введение. Углеродные нанотрубки (УНТ) представляют собой группу перспективных наноматериалов для использования в промышленных и биомедицинских целях. Литературные данные свидетельствуют о влиянии физико-химических особенностей УНТ на реализацию токсических эффектов, в том числе способность вызывать повреждения ДНК и индуцировать апоптоз. В настоящем исследовании проведена сравнительная оценка проапоптотических эффектов и механизмов их реализации при воздействии одностенных и многостенных УНТ российского производства на культурах клеток дыхательной системы человека.</p></sec><sec><title>Материалы и методы</title><p>Материалы и методы. Клетки бронхиального эпителия BEAS-2B, альвеолярного эпителия A549 и фибробластов лёгких MRC5-SV40 человека подвергались экспозиции очищенных и неочищенных от металлических примесей ОУНТ TUBALL™ и МУНТ Таунит-М. В клетках, подвергшихся воздействию 4 концентраций (100; 50; 0,03; 0,0006 мкг/мл) всех типов исследуемых УНТ в течение 72 ч, оценивали уровень мРНК генов P53, BAX и BCL2, а также уровень активных форм кислорода.</p></sec><sec><title>Результаты</title><p>Результаты. Все изученные в эксперименте типы УНТ инициировали апоптоз эпителиальных клеток дыхательной системы человека BEAS-2B и A549, но не фибробластов лёгких MRC5-SV40. BEAS-2B были более чувствительны к воздействию МУНТ, тогда как A549 — к ОУНТ с металлическими включениями. Признаки инициации апоптоза появлялись на низких концентрациях, в том числе соответствовавших производственным экспозициям. Механизм оксидативного стресса может выступать фактором запуска апоптоза в клетках лёгочного эпителия.</p></sec><sec><title>Ограничения исследования</title><p>Ограничения исследования. Относительно короткое (72 ч) время экспозиции  клеток и применение 2D-клеточных моделей, не учитывающих реальные взаимодействия клеток.</p></sec><sec><title>Заключение</title><p>Заключение. Выявлены различия в механизмах реализации внутреннего пути апоптоза и чувствительности к разным типам УНТ в зависимости от вида эпителиальных клеток. Сравнительный анализ инициации апоптоза различными типами УНТ показывает, что существуют различия в потенциальных клетках-мишенях и токсических механизмах, что необходимо учитывать в дальнейших исследованиях.</p><p>Соблюдение этических стандартов. Исследование не требует представления заключения комитета по биомедицинской этике или иных документов.</p></sec><sec><title>Участие авторов</title><p>Участие авторов:Фатхутдинова Л.М. — дизайн исследования, анализ материала, подготовка статьи к публикации; Габидинова Г.Ф. — обзор литературы по теме исследования, культивирование клеток, проведение тестов на клетках, статистическая обработка данных, подготовка статьи к публикации;Димиев А.М. — разработка методов подготовки суспензий материалов для внесения в клетки;Валеева Е.В. — анализ экспрессии генов в клетках;Тимербулатова Г.А. — обзор литературы по теме исследования, культивирование клеток, проведение тестов на клетках, обобщение полученных результатов, подготовка статьи к публикации.Все соавторы — утверждение окончательного варианта статьи, ответственность за целостность всех частей статьи.</p></sec><sec><title>Конфликт интересов</title><p>Конфликт интересов. Авторы декларируют отсутствие явных и потенциальных конфликтов интересов в связи с публикацией данной статьи.</p></sec><sec><title>Финансирование</title><p>Финансирование. Исследование выполнено при поддержке Российского научного фонда № 22-25-00512. https://rscf.ru/project/22-25-00512/</p></sec><sec><title>Поступила</title><p>Поступила: 12.10.2023 / Принята к печати: 15.11.2023 / Опубликована: 08.12.2023</p></sec></abstract><trans-abstract xml:lang="en"><sec><title>Introduction</title><p>Introduction. Carbon nanotubes (CNTs) are a group of promising nanomaterials for industrial and biomedical applications. There has been shown influence of the physicochemical characteristics of CNTs on the toxic effects, including the ability to cause DNA damage and induce apoptosis. In this study, there was carried out a comparative assessment of pro-apoptotic effects under exposure to single-walled and multi-walled CNTs produced in Russia on human respiratory cells.</p></sec><sec><title>Materials and methods</title><p>Materials and methods. Human bronchial epithelial cells BEAS-2B, alveolar epithelial cells A549, and lung fibroblasts MRC5-SV40 were exposed to pristine and purified TUBALL™ SWCNTs and Taunit-M MWCNTs. In cells exposed to 4 concentrations (100, 50, 0.03, 0.0006 μg/ml) of all types of CNTs for 72 hours, the level of mRNA of the P53, BAX and BCL2 genes, as well as the level of reactive oxygen species were assessed.</p></sec><sec><title>Results</title><p>Results. All types of CNTs initiated apoptosis in human respiratory epithelial cells BEAS-2B and A549, but not in MRC5-SV40 lung fibroblasts. BEAS-2B were more sensitive to the effects of MWCNTs, while A549 were more sensitive to pristine SWCNTs. Apoptosis was initiated at low concentrations, including those corresponding to industrial exposures. The mechanism of oxidative stress could act as a factor in triggering apoptosis in lung epithelial cells.</p></sec><sec><title>Limitations</title><p>Limitations. Relatively short (72 hours) cell incubation time and the use of 2D cell models that do not consider real cell interactions.</p></sec><sec><title>Conclusion</title><p>Conclusion. There were revealed differences in the mechanisms of initiation of the internal pathway of apoptosis and sensitivity to different types of CNTs depending on the type of epithelial cells. Comparative analysis of the initiation of apoptosis by different types of CNTs has shown that there are differences in potential target cells and toxic mechanisms, which should be considered in further studies.</p><p>Compliance with ethical standards. The study does not require the submission of a biomedical ethics committee opinion or other documents.</p></sec><sec><title>Contribution</title><p>Contribution:Fatkhutdinova L.M. — research design, data analysis, manuscript writing and editing;Gabidinova G.F. — review of the literature, cell cultivation, cell tests, data processing, manuscript writing;Dimiev A.M. — development of methods for preparing suspensions of materials for introduction into cells;Valeeva E.V. — cell tests (gene expression);Timerbulatova G.A. — review of the literature, cell cultivation, cell tests, summarizing the results obtained manuscript writing.All authors are responsible for the integrity of all parts of the manuscript and approval of the manuscript final version</p></sec><sec><title>Conflict of interest</title><p>Conflict of interest. The authors declare no conflict of interest.</p></sec><sec><title>Acknowledgment</title><p>Acknowledgment. The study was supported by the Russian Science Foundation grant № 22-25-00512, https://rscf.ru/project/22-25-00512/</p></sec><sec><title>Received</title><p>Received: October 12, 2023 / Accepted: November 15, 2023 / Published: December 8, 2023</p></sec></trans-abstract><kwd-group xml:lang="ru"><kwd>углеродные нанотрубки</kwd><kwd>BEAS-2B</kwd><kwd>A549</kwd><kwd>MRC5-SV40</kwd><kwd>апоптоз</kwd><kwd>P53</kwd><kwd>BCL2</kwd><kwd>BAX</kwd><kwd>экспрессия генов</kwd></kwd-group><kwd-group xml:lang="en"><kwd>carbon nanotubes</kwd><kwd>BEAS-2B</kwd><kwd>A549</kwd><kwd>MRC5-SV40</kwd><kwd>apoptosis</kwd><kwd>P53</kwd><kwd>BCL2</kwd><kwd>BAX</kwd><kwd>gene expression</kwd></kwd-group></article-meta></front><back><ref-list><title>References</title><ref id="cit1"><label>1</label><citation-alternatives><mixed-citation xml:lang="ru">Eatemadi A., Daraee H., Karimkhanloo H., Kouhi M., Zarghami N., Akbarzadeh A., et al. 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