Advances in Molecular OncologyAdvances in Molecular OncologyУспехи молекулярной онкологии2313-805X2413-3787Publishing House ABV Press22910.17650/2313-805X-2019-6-3-8-27REVIEW ARTICLESОБЗОРНЫЕ СТАТЬИModern approaches for the screening of epigenetically active xenobioticsСовременные подходы к выявлению и изучению эпигенетически активных ксенобиотиковhttps://orcid.org/0000-0003-0896-2952MaksimovaV. P.МаксимоваВ. П.
Russian Federation

24 Kashirskoe Shosse, Moscow 115478

115478 Москва, Каширское шоссе, 24

BugaevaP. E.БугаеваП. Е.
Russian Federation

Build. 2, 8 Trubetskaya St., Moscow 119991

119991 Москва, ул. Трубецкая, 8, стр. 2

ZhidkovaE. M.ЖидковаЕ. М.
Russian Federation

24 Kashirskoe Shosse, Moscow 115478

115478 Москва, Каширское шоссе, 24

UsalkaO. G.УсалкаО. Г.
Russian Federation

Build. 2, 8 Trubetskaya St., Moscow 119991

119991 Москва, ул. Трубецкая, 8, стр. 2

https://orcid.org/0000-0002-1967-9637LesovayaE. A.ЛесоваяЕ. А.
Russian Federation

24 Kashirskoe Shosse, Moscow 115478, 

9 Vysokovol’tnaya St., Ryazan 390026

115478 Москва, Каширское шоссе, 24, 

390026 Рязань, ул. Высоковольтная, 9

BelitskyG. A.БелицкийГ. А.
Russian Federation

24 Kashirskoe Shosse, Moscow 115478

115478 Москва, Каширское шоссе, 24

https://orcid.org/0000-0002-9710-8178YakubovskayaM. G.ЯкубовскаяМ. Г.
Russian Federation

24 Kashirskoe Shosse, Moscow 115478

115478 Москва, Каширское шоссе, 24

https://orcid.org/0000-0002-8599-6833KirsanovK. I.КирсановК. И.
Russian Federation

24 Kashirskoe Shosse, Moscow 115478, 

6 Miklukho-Maklayа St., Moscow 117198

Кирилл Игоревич Кирсанов

115478 Москва, Каширское шоссе, 24, 

117198 Москва, ул. Миклухо-Маклая, 6

kkirsanov85@yandex.ruN.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of RussiaФГБУ «Национальный медицинский исследовательский центр онкологии им. Н. Н. Блохина» Минздрава РоссииSechenov First Moscow State Medical University, Ministry of Health of RussiaФГАОУ ВО Первый Московский государственный медицинский университет им. И. М. Сеченова Минздрава России (Сеченовский университет)I.P. Pavlov Ryazan State Medical UniversityФГБОУ ВО «Рязанский государственный медицинский университет им. И. П. Павлова»Peoples’ Friendship University of RussiaФГАОУ ВО «Российский университет дружбы народов»15092019638270811201908112019Copyright ©; 2019, Maksimova V.P., Bugaeva P.E., Zhidkova E.M., Usalka O.G., Lesovaya E.A., Belitsky G.A., Yakubovskaya M.G., Kirsanov K.I.Copyright ©; 2019, Максимова В.П., Бугаева П.Е., Жидкова Е.М., Усалка О.Г., Лесовая Е.А., Белицкий Г.А., Якубовская М.Г., Кирсанов К.И.2019Maksimova V.P., Bugaeva P.E., Zhidkova E.M., Usalka O.G., Lesovaya E.A., Belitsky G.A., Yakubovskaya M.G., Kirsanov K.I.Максимова В.П., Бугаева П.Е., Жидкова Е.М., Усалка О.Г., Лесовая Е.А., Белицкий Г.А., Якубовская М.Г., Кирсанов К.И.https://creativecommons.org/licenses/by/4.0https://umo.abvpress.ru/jour/article/view/229

Objective. Review of the modern methodological approaches for testing and studying the epigenetic activity of xenobiotics.

Materials and methods. In preparing the review, we used information databases of biomedical literature SciVerse Scopus (538), PubMed (746), Web of Science (625), RSCI (45). To obtain full-text documents, electronic resources of PubMed Central (PMC), Research Gate, RSCI, CyberLeninka were used. In the text of the review, 87 modern publications (2010–2019) were cited, as well as 17 earlier articles published by the founders of the methods, which are used today.

Results. In the review, current data on epigenetic regulation for gene expression at the level of DNA methylation and histone modification are discussed, in vitro model systems and model organisms are described, and modern methods for screening of epigenetically active xenobiotics are presented.

Conclusion. Modern data concerning the mechanisms of epigenetic regulation of gene expression, the usage of existing model systems and model organisms, as well as the application of various methodological approaches and techniques, allow extensive screening of xenobiotics (including drugs and compounds synthesized for national economic tasks) for epigenetic activity. The identification of epigenetically active compounds is important in terms of improving the prevention and treatment of a number of diseases and, in particular, malignant neoplasms.

Цель исследования – анализ существующих методических подходов к тестированию и изучению эпигенетической активности ксенобиотиков.

Материалы и методы. При подготовке обзора были использованы информационные базы биомедицинской литературы SciVerse Scopus (538), PubMed (746), Web of Science (625), РИНЦ (45). Для получения полнотекстовых документов использованы электронные ресурсы PubMed Central (PMC), Research Gate, РИНЦ, КиберЛенинка. В тексте обзора процитированы 87 современных публикаций (2010–2019 гг.), а также 17 статей основоположников анализируемых в обзоре методик, которые используются и в наши дни.

Результаты. В обзоре рассмотрены современные данные по основным закономерностям функционирования системы регуляции экспрессии генов на уровне метилирования ДНК и модификации гистонов, описаны модельные организмы, используемые как при тестировании ксенобиотиков на эпигенетическую активность, так и для детального изучения их конкретных эффектов на отдельные механизмы эпигенетической регуляции транскрипции. Поскольку в настоящее время не разработаны тест-системы, позволяющие интегрально оценить эффекты ксенобиотиков на эпигенетическую систему регуляции транскрипции, в обзоре представлены методы оценки выявления влияний различных факторов окружающей среды, в том числе различных ксенобиотиков, на метилирование ДНК и модификацию гистонов.

Заключение. Современные представления о механизмах эпигенетической регуляции экспрессии генов, использование существующих модельных систем и модельных организмов, а также применение различных методологических и методических подходов позволяют проводить широкое тестирование ксенобиотиков, в том числе медицинских препаратов и соединений, синтезированных для выполнения народнохозяйственных задач, на эпигенетическую активность. Выявление эпигенетически активных соединений важно в плане совершенствования профилактики и лечения ряда заболеваний и, прежде всего, злокачественных новообразований.

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