medlitГигиена и санитарияHygiene and Sanitation0016-99002412-0650Federal Scientific Center of Hygiene named after F.F. Erisman10.47470/0016-9900-2024-103-10-1251-1256ngqwicmedlit-4428Research ArticleПРОФИЛАКТИЧЕСКАЯ ТОКСИКОЛОГИЯ И ГИГИЕНИЧЕСКОЕ НОРМИРОВАНИЕPREVENTIVE TOXICOLOGY AND HYGIENIC STANDARTIZATIONАнализ генотоксичности нанокомпозита железа арабиногалактана методом ДНК-кометAnalysis of the genotoxicity of iron nanocomposite arabinogalactan using the DNA comet methodhttps://orcid.org/0000-0002-9406-5424ТютринаВера АлександровнаTyutrinaVera A.

Канд. фарм. наук, науч. сотр. лаб. биомоделирования и трансляционной медицины ФГБНУ ВСИМЭИ, 665827, Ангарск, Россия

e-mail: tyutrina.v.a@yandex.ru

PhD (Pharm.), researcher of the Laboratory of biomodelling and translational medicine of the East-Siberian Institute of Medical and Ecological Research, Angarsk, 665827, Russian Federation

e-mail: tyutrina.v.a@yandex.ru

tyutrina.v.a@yandex.ruhttps://orcid.org/0000-0003-1052-4601СоседоваЛариса МихайловнаSosedovaLarisa M.

Доктор мед. наук, профессор, зав. лаб. биомоделирования и трансляционной медицины ФГБНУ ВСИМЭИ, 665827, Ангарск, Россия

e-mail: sosedlar@mail.ru

DSc (Med.), Prof., head of the Laboratory of biomodelling and translational medicine of the East-Siberian Institute of Medical and Ecological Research, Angarsk, 665827, Russian Federation

e-mail: sosedlar@mail.ru

sosedlar@mail.ruhttps://orcid.org/0000-0002-6100-6292НовиковМихаил АлександровичNovikovMikhail A.

Канд. биол. наук, ст. науч. сотр. лаб. биомоделирования и трансляционной медицины ФГБНУ ВСИМЭИ, 665827, Ангарск, Россия

e-mail: novik-imt@mail.ru

PhD (Biol.), senior researcher of the Laboratory of biomodelling and translational medicine of the East-Siberian Institute of Medical and Ecological Research, Angarsk, 665827, Russian Federation

e-mail: novik-imt@mail.ru

novik-imt@mail.ruФГБНУ «Восточно-Сибирский институт медико-экологических исследований»РоссияEast-Siberian Institute of Medical and Ecological ResearchRussian Federation2024191120241031012511256Copyright © Тютрина В.А., Соседова Л.М., Новиков М.А., 20242024Тютрина В.А., Соседова Л.М., Новиков М.А.Tyutrina V.A., Sosedova L.M., Novikov M.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.rjhas.ru/jour/article/view/4428Введение

Введение. Для успешного внедрения в практику железосодержащих наночастиц необходимо понимать их влияние на здоровье человека. Одним из важнейших этапов определения безопасности железосодержащих наночастиц в составе нанокомпозитов является исследование их генотоксических свойств как после экспозиции, так и в отдалённом периоде.

Материалы и методы

Материалы и методы. Самцам белых крыс перорально вводили в течение 10 дней водный раствор нанокомпозита Fe арабиногалактана в дозах 500 и 5000 мкг/кг. Образцы крови брали из хвостовой вены. Оценку генотоксического эффекта нанокомпозита Fe арабиногалактана на лейкоциты проводили по процентному содержанию ДНК в хвосте ДНК-комет в три срока методом ДНК-комет в щелочной версии: на следующие сутки после окончания экспозиции, через два и четыре месяца для выявления сохранения или отсутствия эффекта.

Результаты

Результаты. В представленном исследовании на всех этапах эксперимента не выявлено статистически значимого увеличения повреждений ДНК при применении исследуемого нанокомпозита в дозе 500 мкг/кг. При этом было обнаружено, что нанокомпозит Fe арабиногалактан оказывает негативное воздействие на структуру ДНК в дозе 5000 мкг/кг через сутки после экспозиции.

Ограничения исследования

Ограничения исследования. Эксперимент ограничен исследованием генотоксического эффекта нанокомпозита Fe арабиногалактана в дозах 500 и 5000 мкг/кг на самцах белых крыс на следующие сутки после десятидневной экспозиции и в отдалённом периоде через два и четыре месяца.

Заключение

Заключение. Установлено, что статистически значимые повреждения ДНК клеток крови вызывает применение только нанокомпозита Fe арабиногалактана сразу после экспозиции и в наиболее высокой концентрации 5000 мкг/кг, со временем же возникшие повреждения ДНК нивелируются системами репарации. Следовательно, потенциальный генотоксический эффект при применении исследуемого нанокомпозита для клеток крови весьма невысок.

Соблюдение этических стандартов. Исследование одобрено локальным этическим комитетом ФГБНУ ВСИМЭИ (протокол № 1 от 18.12.2017 г.), проведено в соответствии с Европейской конвенцией о защите позвоночных животных, используемых для экспериментов или в иных научных целях (ETS N 123), директивой Европейского парламента и Совета Европейского союза 2010/63/EC от 22.09.2010 г. о защите животных, используемых для научных целей.

Участие авторов

Участие авторов: Тютрина В.А. — концепция и дизайн исследования, сбор и обработка данных, статистическая обработка данных, написание текста, редактирование; Соседова Л.М. — концепция и дизайн исследования, редактирование; Новиков М.А. — концепция и дизайн исследования. Все соавторы — утверждение окончательного варианта статьи, ответственность за целостность всех частей статьи.

Конфликт интересов

Конфликт интересов. Авторы декларируют отсутствие явных и потенциальных конфликтов интересов в связи с публикацией данной статьи.

Финансирование

Финансирование. Работа выполнена по плану НИР в рамках государственного задания.

Поступила

Поступила: 10.08.2024 / Поступила после доработки: 30.09.2024 / Принята к печати: 02.10.2024 / Опубликована: 19.11.2024

Introduction

Introduction. Successful implementation of iron-containing nanoparticles into practice requires obtaining knowledge about their effect on human health. One of the most important stages in developing an understanding of the safety of iron-containing nanoparticles in nanocomposites is the study of their genotoxic properties both after exposure and over the long-term period.

The aim of the study is to assess DNA damage in nucleated blood cells in white rats during subacute administration of the Fe nanocomposite arabinogalactan in two different doses one day after exposure, and in 2 and 4 months.

Materials and methods

Materials and methods. Male white rats were orally administered an aqueous solution of Fe arabinogalactan nanocomposite at doses of 500 µg/kg and 5000 µg/kg for 10 days. Blood samples were taken from the tail vein. The genotoxic effect of Fe arabinogalactan nanocomposite on leukocytes was assessed by the percentage of DNA in the «DNA comet tail» at 3 times using the alkaline version of the DNA comet assay: on the next day after the end of exposure, and in 2 and 4 months to determine whether the effect was preserved or absent.

Results

Results. In the present study, no statistically significant increase in DNA damage was detected at any stage of the experiment when using the studied nanocomposite at a dose of 500 µg/kg. At the same time, Fe arabinogalactan nanocomposite was found to have a negative effect on the DNA structure at a dose of 5000 µg/kg one day after exposure.

Limitations

Limitations. The experiment is limited to studying the genotoxic effect of the Fe arabinogalactan nanocomposite at doses of 500 and 5000 µg/kg on male white rats the next day after ten-day exposure and in the late period after 2 and 4 months.

Conclusions

Conclusions. Statistically significant damage to the DNA of blood cells has been established to be caused by the use of only nFe-AG immediately after exposure and at the highest concentration of 5000 µg/kg; over time, the resulting DNA damage is leveled out by repair systems. Consequently, the potential genotoxic effect when using the studied nanocomposite for blood cells is very weak.

Compliance with ethical standards. The study was approved by the local ethics committee of the East-Siberian Institute of Medical and Ecological Research (Protocol No.1 of 12/18/2017), conducted in accordance with the European Convention for the Protection of Vertebrate Animals Used for Experiments or for Other Scientific Purposes (ETS N 123), Directive 2010/63/EC of the European Parliament and the Council of 22.09.2010 on the protection of animals used for scientific purposes.

Contribution

Contribution: Tyutrina V.A. — concept and design of research, data collection and processing, statistical data processing, text writing, editing; Sosedova L.M. — concept and design of research, editing; Novikov M.A. — concept and design of research. All authors are responsible for the integrity of all parts of the manuscript and approval of the manuscript final version.

Conflict of interest

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

Acknowledgment

Acknowledgment. The work was carried out according to the research plan within the framework of the state task.

Received

Received: August 10, 2024 / Revised: September 30, 2024 / Accepted: October 2, 2024 / Published: November 19, 2024

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