toxreviewТоксикологический вестникToxicological Review0869-79223034-4611Federal Scientific Center of Hygiene named after F.F. Erisman10.47470/0869-7922-2026-34-1-5-15sxhqvvtoxreview-1061Research ArticleПРОФИЛАКТИЧЕСКАЯ ТОКСИКОЛОГИЯPREVENTIVE TOXICOLOGYПодходы к оценке in vitro генотоксичного потенциала наноматериалов (на примере углеродных нанотрубок)Approaches to the in vitro assessment of the genotoxic potential of carbon nanotubeshttps://orcid.org/0000-0001-9506-563XФатхутдиноваЛилия МинвагизовнаFatkhutdinovaLiliya M.

Доктор медицинских наук, заведующий кафедрой гигиены, медицины труда ФГБОУ ВО Казанский государственный медицинский университет Минздрава России, 420012, г. Казань, Россия

e-mail: liliya.fatkhutdinova@kazangmu.ru

MD, Professor, Head of the Department of Hygiene and Occupational Medicine, Kazan State Medical University of the Ministry of Health of the Russian Federation, Kazan, 420012, Russian Federation

e-mail: liliya.fatkhutdinova@kazangmu.ru

liliya.fatkhutdinova@kazangmu.ruhttps://orcid.org/0000-0002-2479-2474ТимербулатоваГюзель АбдулхалимовнаTimerbulatovaGyuzel A.

Доцент кафедры гигиены, медицины труда ФГБОУ ВО Казанский ГМУ Минздрава России, 420012,  г. Казань, Россия

e-mail: guzel.timerbulatova@kazangmu.ru

Senior Lecturer at the Department of Hygiene and Occupational Medicine, Kazan State Medical University of the Ministry of Health of the Russian Federation, Kazan, 420012, Russian Federation

e-mail: guzel.timerbulatova@kazangmu.ru

guzel.timerbulatova@kazangmu.ruhttps://orcid.org/0000-0003-2616-5017ГабидиноваГульназ ФаезовнаGabidinovaGulnaz F.

Ассистент кафедры гигиены, медицины труда ФГБОУ ВО Казанский ГМУ Минздрава России, 420012, г. Казань, Россия

e-mail: gabidinova26@kazangmu.ru

Assistant of the Department of Hygiene and Occupational Medicine, Kazan State Medical University of the Ministry of Health of the Russian Federation, Kazan, 420012, Russian Federation

e-mail: gabidinova26@kazangmu.ru

gabidinova26@kazangmu.ruФГБОУ ВО «Казанский государственный медицинский университет» Минздрава РоссииРоссияKazan State Medical University of the Ministry of Health of the Russian FederationRussian Federation202618032026341515Copyright © Фатхутдинова Л.М., Тимербулатова Г.А., Габидинова Г.Ф., 20262026Фатхутдинова Л.М., Тимербулатова Г.А., Габидинова Г.Ф.Fatkhutdinova L.M., Timerbulatova G.A., Gabidinova G.F.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.toxreview.ru/jour/article/view/1061Введение

Введение. Углеродные нанотрубки (УНТ) – высокотехнологичные материалы, однако их генотоксический и канцерогенный потенциал изучен недостаточно. Для оценки генотоксичности УНТ необходимы альтернативные методы in vitro, разработка которых невозможна без предварительного изучения механизмов повреждения ДНК.

Материал и методы

Материал и методы. Исследование проведено на 2D- и 3D-культурах клеток дыхательной системы человека. Исследованы эффекты российских одностенных (ОУНТ TUBALL™, очищенные и неочищенные) и многостенных (МУНТ «Таунит-М») УНТ. Цитотоксичность УНТ оценивали с помощью MTS-теста и анализа лактатдегидрогеназы (ЛДГ). Генотоксический потенциал исследовали методом ДНК-комет. Локализацию УНТ в клетках определяли методом просвечивающей электронной микроскопии. Для выявления окислительного стресса измеряли уровень активных форм кислорода (АФК) с использованием набора DCFDA. Профиброгенную и проапоптотическую активность УНТ определяли по экспрессии генов (TGF-β1, P53, Bax, Bcl2) методом ПЦР в реальном времени.

Результаты

Результаты. Наибольшую чувствительность к цитотоксичности УНТ показали фибробласты, наименьшую – клетки A549. Генотоксичность УНТ выявлена на всех клетках при концентрации 20 мкг/мл. Все УНТ проникали в клетки, МУНТ обнаруживались в ядре клеток. Окислительный стресс дозозависимо индуцировался всеми типами УНТ, неочищенные ОУНТ вызывали наиболее выраженный эффект. В клетках BEAS-2B МУНТ вызывали повышение экспрессии TGF-β1 при низких концентрациях, в то время как ОУНТ вызывали аналогичный эффект лишь при высокой концентрации.  В клетках A549 все типы УНТ проявляли профиброгенный эффект во всех концентрациях. В фибробластах значимого повышения экспрессии гена TGF-β1 не наблюдалось. В клетках BEAS-2B и A549 УНТ демонстрировали способность к инициации апоптотических сигнальных путей, в MRC5-SV40 признаков апоптоза в ответ на воздействие УНТ не выявлено. Исследования на 3D-моделях клеточных культур продемонстрировали признаки окислительного стресса в ответ на воздействие УНТ, проапоптотических и профиброгенных эффектов УНТ обнаружено не было.

Заключение

Заключение. Генотоксичность УНТ определяется их типом и видом клеток-мишеней, проявляясь в субтоксическом диапазоне концентраций. Ключевые механизмы включают окислительный стресс, прямое повреждение ДНК и индукцию апоптоза. Результаты, полученные на 3D-моделях, демонстрируют меньшую чувствительность, что может указывать на защитную роль тканевой организации.

Ограничения исследования

Ограничения исследования. В рамках данной работы не оценивалась возможная роль репарации ДНК. Исследование охватывает ограниченное число конкретных типов отечественных УНТ.

Соблюдение этических стандартов. Исследование не требует предоставления заключения комитета по биомедицинской этике или иных документов.

Участие авторов

Участие авторов: Фатхутдинова Л.М. – дизайн исследования, анализ материала, редактирование; Тимербулатова Г.А. –  культивирование клеток, проведение тестов на клетках, обобщение полученных результатов, редактирование; Габидинова Г.Ф. – разработка подходов культивирования трёхмерных моделей, проведение тестов на клетках, обзор литературы, статистическая обработка данных, обобщение полученных результатов. Все соавторы – утверждение окончательного варианта статьи, ответственность за целостность всех её частей.

Конфликт интересов

Конфликт интересов. Авторы заявляют об отсутствии явных и потенциальных конфликтов интересов в связи  с публикацией данной статьи.

Финансирование

Финансирование. Исследование выполнено при поддержке Российского научного фонда № 22-25-00512. https://rscf.ru/project/22-25-00512/

Поступила в редакцию

Поступила в редакцию: 22 января 2026 / Принята в печать: 02 февраля 2026 / Опубликована: 18 марта 2026

 

 

Introduction

Introduction. Carbon nanotubes (CNTs) are high-tech materials, but their genotoxic and carcinogenic potential has not been sufficiently studied. To assess the genotoxicity of CNTs, alternative in vitro methods are needed, the development of which is impossible without a preliminary study of DNA damage mechanisms.

Material and methods

Material and methods. The study was conducted on 2D and 3D human respiratory cell cultures. The effects of Russian single-wall (SWCNT TUBALL™, purified and unpurified) and multi-wall (MWCNT Taunit-M) CNTs were investigated. The cytotoxicity of CNTs was assessed using the MTS assay and lactate dehydrogenase (LDH) assay. The genotoxic potential was investigated using the DNA comet method. The localization of CNTs in cells was determined by transmission electron microscopy. To detect oxidative stress, reactive oxygen species (ROS) levels were measured using a DCFDA kit. The pro-fibrogenic and pro-apoptotic activities of CNTs were determined by assessing gene expression (TGF-β1, P53, Bax, Bcl2) using real-time PCR.

Results

Results. Fibroblasts demonstrated the highest sensitivity to CNT cytotoxicity, while A549 cells demonstrated the lowest. CNT genotoxicity was detected in all cells at a concentration of 20 µg/ml. All CNTs penetrated the cells, and MWCNTs were detected in the cell nucleus. Oxidative stress was induced dose-dependently by all types of CNTs, with unpurified SWCNTs producing the most pronounced effect. In BEAS-2B cells, MWCNTs induced an increase in TGF-β1 expression at low concentrations, while SWCNTs induced a similar effect only at high concentrations. In A549 cells, all types of CNTs exhibited a pro-fibrogenic effect at all concentrations. In fibroblasts, no significant increase in TGF-β1 gene expression was observed. In BEAS-2B and A549 cells, CNTs demonstrated the ability to initiate apoptotic signaling pathways, while in MRC5-SV40 cells, no signs of apoptosis in response to CNTs were detected. Studies in 3D cell culture models demonstrated signs of oxidative stress in response to CNTs; no pro-apoptotic or pro-fibrogenic effects of CNTs were detected.

Limitations

Limitations. The possible role of DNA repair was not assessed in this study. The study covers a limited number of specific types of domestically produced CNTs.

Conclusion

Conclusion. The genotoxicity of CNTs is determined by their type and type of target cells, manifesting itself in a subtoxic concentration range. Key mechanisms include oxidative stress, direct DNA damage, and induction of apoptosis. The results obtained on 3D models demonstrate lower sensitivity, which may indicate a protective role of the tissue organization.

Compliance with ethical standards. The study does not require a biomedical ethics committee opinion or other documents.

Authors’ contribution

Authors’ contribution: Fatkhutdinova L.M. – study design, analysis of material, editing; Timerbulatova G.A. – cell culturing, cell testing, summarizing the results, editing; Gabidinova G.F. – development of approaches for culturing 3D models, cell testing, literature review, statistical data processing, summarizing the results. All co-authors approved the final version of the article and are responsible for the integrity of all parts of the article.

Conflict of interest

Conflict of interest. The authors declare no apparent and potential conflicts of interest in relation to the publication of this article.

Funding

Funding. The study was supported by the Russian Science Foundation grant No. 22-25-00512. https://rscf.ru/project/22-25-00512/

Received

Received: January 22, 2026 / Accepted: February 2, 2026 / Published: March 18, 2026

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The authors declare that there are no conflicts of interest present.