medlitГигиена и санитарияHygiene and Sanitation0016-99002412-0650Federal Scientific Center of Hygiene named after F.F. Erisman10.47470/0016-9900-2023-102-11-1224-1227pgrkfdmedlit-3533Research ArticleПРОФИЛАКТИЧЕСКАЯ ТОКСИКОЛОГИЯ И ГИГИЕНИЧЕСКОЕ НОРМИРОВАНИЕPREVENTIVE TOXICOLOGY AND HYGIENIC STANDARTIZATIONЭкспрессия генов CDKN1A, MDM2 и ATM как биомаркер токсического действия тяжёлых металлов (обзор литературы)Expression of the CDKN1A, MDM2, and ATM genes as a biomarker of the toxic effect of heavy metals (literature review)https://orcid.org/0000-0002-7029-3406ШаиховаДарья РамильевнаShaikhovaDaria R.

Науч. сотр. отдела молекулярной биологии и электронной микроскопии ФБУН «Екатеринбургский медицинский научный центр профилактики и охраны здоровья рабочих промышленных предприятий» Роспотребнадзора, 620014, Екатеринбург

e-mail: darya.boo@mail.ru

Research Scientist, Department of Molecular Biology and Electron Microscopy, Yekaterinburg Medical Research Center for Prophylaxis and Health Protection in Industrial Workers, Yekaterinburg, 620014, Russian Federation

e-mail: darya.boo@mail.ru

darya.boo@mail.ruhttps://orcid.org/0000-0001-8794-7288АмроминаАнна МихайловнаAmrominaAnna M.

Мл. науч. сотр. отдела молекулярной биологии и электронной микроскопии ФБУН «Екатеринбургский медицинский научный центр профилактики и охраны здоровья рабочих промышленных предприятий» Роспотребнадзора, 620014, Екатеринбург

e-mail: amrominaam@ymrc.ru

amrominaam@ymrc.ruhttps://orcid.org/0000-0002-4109-9268БерёзаИван АндреевичBerezaIvan A.

Науч. сотр. отдела молекулярной биологии и электронной микроскопии ФБУН «Екатеринбургский медицинский научный центр профилактики и охраны здоровья рабочих промышленных предприятий» Роспотребнадзора, 620014, Екатеринбург

e-mail: berezaia@ymrc.ru

berezaia@ymrc.ruФБУН «Екатеринбургский медицинский научный центр профилактики и охраны здоровья рабочих промпредприятий» Федеральной службы по надзору в сфере защиты прав потребителей и благополучия человекаРоссияYekaterinburg Medical Research Center for Prophylaxis and Health Protection in Industrial WorkersRussian Federation2023131220231021112241227Copyright © Шаихова Д.Р., Амромина А.М., Берёза И.А., 20232023Шаихова Д.Р., Амромина А.М., Берёза И.А.Shaikhova D.R., Amromina A.M., Bereza I.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/3533

Разработка новых подходов, которые позволят дифференцировать широкий спектр токсических эффектов, поможет значительно улучшить оценку риска. Для понимания механизмов ответа на молекулярном уровне важно изучение экспрессии генов, отвечающих за репарацию ДНК, так как данный процесс является одним из ранних ответов на токсическое действие.

Цель исследования — обобщение имеющихся данных об экспрессии генов репарации (CDKN1A, MDM2 и ATM) в рамках токсического эффекта воздействия тяжёлых металлов.

Проведён систематический поиск для выявления исследований по заданной теме в электронных базах данных PubMed, Web of Science, eLIBRARY и Google Scholar. Для поиска использовались следующие ключевые слова: heavy metals, CDKN1A, MDM2, ATM, toxicity, DNA repair, gene expression. Поиск научных публикаций осуществлялся независимо тремя авторами, все найденные статьи проверялись и сравнивались для отсеивания дублирующихся статей. В данный обзор включено 50 литературных источников.

Анализ токсикогеномных исследований позволил выделить несколько генов для оценки токсичности тяжёлых металлов среди большого количества биомаркеров-кандидатов. Наиболее часто рассматриваемыми генами являются ген p21/CDKN1A, протоонкоген MDM2 и ген ATM.

Ограничения исследования

Ограничения исследования. Ограничением данного обзора является рассмотрение изменения экспрессии лишь небольшого числа генов, отвечающих за репарацию ДНК.

Заключение

Заключение. Таким образом, экспрессия вышеперечисленных генов биомаркеров даёт детальную картину реакции биологической системы на воздействие вредных факторов и может применяться в рамках оценки токсического действия.

Участие авторов

Участие авторов. Все соавторы внесли равнозначный вклад в исследование и подготовку статьи к публикации, прочли и одобрили финальную версию перед публикацией.

Конфликт интересов

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

Финансирование

Финансирование. Исследование не имело спонсорской поддержки.

Поступила

Поступила: 09.10.2023 / Принята к печати: 15.11.2023 / Опубликована: 08.12.2023

The development of new approaches enabling differentiation of a wide range of toxic effects can significantly improve risk assessment. To understand the response mechanisms at the molecular level, it is important to study the expression of genes responsible for DNA repair, since this process is one of the early responses to toxic effects.

The purpose of the study was to summarize available data on the expression of repair CDKN1A, MDM2, and ATM genes associated with toxic effects of exposure to heavy metals.

A systematic search was carried out to identify studies on a given topic in the PubMed, Web of Science, eLIBRARY and Google Scholar electronic databases using the following keywords: heavy metals, CDKN1A, MDM2, ATM, toxicity, DNA repair, and gene expression. The initial search for scientific publications was carried out independently by three authors; then all sources found were checked and compared to filter out duplicate papers. This review covers 50 literature sources.

The analysis of toxicogenome studies allowed us to identify several genes for assessing heavy metal toxicity among a large number of candidate biomarkers. The most commonly considered genes are the p21/CDKN1A gene, the MDM2 proto-oncogene, and the ATM gene.

Limitations

Limitations. The review is limited to considering changes in the expression of only a small number of genes responsible for DNA repair.

Conclusion

Conclusion. The expression of the above biomarker genes provides a detailed picture of the response of a biological system to hazardous exposures and can be used as part of the assessment of toxic effects.

Contributions

Contributions. All co-authors made a significant contribution to the development of concept, research and preparation of the article, read and approved its final version before publication.

Conflict of interest

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

Acknowledgement

Acknowledgement. The study had no sponsorship.

Received

Received: October 9, 2023 / Accepted: November 15, 2023 / Published: December 8, 2023

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