toxreviewТоксикологический вестникToxicological Review0869-79223034-4611Federal Scientific Center of Hygiene named after F.F. Erisman10.47470/0869-7922-2026-34-1-27-36ikmcpptoxreview-1063Research ArticleПРОФИЛАКТИЧЕСКАЯ ТОКСИКОЛОГИЯPREVENTIVE TOXICOLOGYПроблемы выявления эпигенетически активных негенотоксичных канцерогеновChallenges in the detection of epigenetically active non-genotoxic carcinogenshttps://orcid.org/0000-0002-9710-8178ЯкубовскаяМарианна ГеннадиевнаYakubovskayaMarianna G.

Доктор медицинских наук, заведующая отделом молекулярных механизмов канцерогенеза НИИ экспериментальной онкологии и канцерогенеза; профессор кафедры последипломного образования врачей департамента профессионального образования ФГБУ «НМИЦ онкологии им. Н.Н. Блохина» Минздрава России 115522, Москва, Россия; главный научный сотрудник НИИ молекулярной и клеточной медицины МИ ФГАОУ ВО РУДН им. Патриса Лумумбы, 117198, Москва, Россия

e-mail: mgyakubovskaya@mail.ru

MD, PhD, Head of the Department of Molecular Mechanisms of Carcinogenesis, Research Institute of Experimental Oncology and Carcinogenesis; Professor, Department of Postgraduate Medical Education, Department of Professional Education, N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of the Russian Federation, Moscow, 115522, Russian Federation; Chief Researcher, Research Institute of Molecular and Cellular Medicine, Peoples’ Friendship University of Russian Federation, Moscow, 117198, Russian Federation

e-mail: mgyakubovskaya@mail.ru

mgyakubovskaya@mail.ruhttps://orcid.org/0000-0003-0896-2952МаксимоваВарвара ПавловнаMaksimovaVarvara P.

Младший научный сотрудник лаборатории канцерогенных веществ отдела изучения молекулярных механизмов канцерогенеза НИИ экспериментальной онкологии и канцерогенеза ФГБУ «НМИЦ онкологии им. Н.Н. Блохина» Минздрава России, 115522, Москва, Россия

e-mail: lavarvar@gmail.com

Junior Researcher, Laboratory of Carcinogens, Department of Molecular Mechanisms of Carcinogenesis, Research Institute of Experimental Oncology and Carcinogenesis, N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of the Russian Federation, Moscow, 115522, Russian Federation

e-mail: lavarvar@gmail.com

lavarvar@gmail.comhttps://orcid.org/0000-0002-3167-7204БелицкийГеннадий АльтеровичBelitskyGennady A.

Главный научный консультант отдела молекулярных механизмов канцерогенеза НИИ экспериментальной онкологии и канцерогенеза; профессор кафедры последипломного образования врачей департамента профессионального образования ФГБУ «НМИЦ онкологии им. Н.Н. Блохина», 115522, Москва, Россия

e-mail: belitsga@gmail.com

Chief Scientific Advisor, Department of Molecular Mechanisms of Carcinogenesis, Research Institute of Experimental Oncology and Carcinogenesis; Professor, Department of Postgraduate Medical Education, Department of Professional Education, N.N. Blokhin National Medical Research Center of Oncology, Moscow, 115522, Russian Federation

e-mail: belitsga@gmail.com

belitsga@gmail.comhttps://orcid.org/0000-0002-8599-6833КирсановКирилл ИгоревичKirsanovKirill I.

Доктор биологических наук, заведующий лабораторией канцерогенных веществ отделом изучения молекулярных механизмов канцерогенеза НИИ экспериментальной онкологии и канцерогенеза; доцент кафедры последипломного образования врачей департамента профессионального образования ФГБУ «НМИЦ онкологии им. Н.Н. Блохина», 115522, Москва, Россия; профессор кафедры общей врачебной практики Медицинского института ФГАОУ ВО «Российский университета дружбы народов им. Патриса Лумумбы», 117198, Москва, Россия

e-mail: kkirsanov85@yandex.ru

Doctor of Biological Sciences, Head of the Laboratory of Carcinogens, Department of Molecular Mechanisms of Carcinogenesis, Research Institute of Experimental Oncology and Carcinogenesis; Associate Professor, Department of Postgraduate Education of Physicians, Department of Professional Education, N.N. Blokhin National Medical Research Center of Oncology, Moscow, 115522, Russia; Professor, Department of General Medical Practice, Medical Institute, Peoples’ Friendship University of Russian Federation, Moscow, 117198, Russian Federation

e-mail: kkirsanov85@yandex.ru

kkirsanov85@yandex.ruНаучно-исследовательский институт экспериментальной онкологии и канцерогенеза ФГБУ «национальный медицинский исследовательский центр онкологии имени Н.Н. Блохина» Минздрава России; Медицинский институт, ФГАОУ ВО «Российский университет дружбы народов имени Патриса Лумумбы»РоссияResearch Institute of Experimental Oncology and Carcinogenesis, N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of the Russian Federation; Medical Institute, Peoples’ Friendship University of RussiaRussian FederationНаучно-исследовательский институт экспериментальной онкологии и канцерогенеза ФГБУ «национальный медицинский исследовательский центр онкологии имени Н.Н. Блохина» Минздрава РоссииРоссияResearch Institute of Experimental Oncology and Carcinogenesis, N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of the Russian FederationRussian Federation2026180320263412736Copyright © Якубовская М.Г., Максимова В.П., Белицкий Г.А., Кирсанов К.И., 20262026Якубовская М.Г., Максимова В.П., Белицкий Г.А., Кирсанов К.И.Yakubovskaya M.G., Maksimova V.P., Belitsky G.A., Kirsanov K.I.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.toxreview.ru/jour/article/view/1063Введение

Введение. Одна из причин наблюдаемого роста заболеваемости злокачественными новообразованиями – отсутствие контроля распространения негенотоксичных канцерогенов.

Цель представленного обзора – анализ проблем в тестировании негенотоксичных канцерогенов и путей создания адекватных подходов к их выявлению посредством анализа эпигенетической активности соединений.

Материал и методы

Материал и методы. Проведён анализ более 200 научных публикаций по теме выявления канцерогенной опасности. Использованы базы данных PubMed (149), Scopus (62), Web of Science (33), ResearchGate (15), РИНЦ (12). На основе анализа отобраны 50 наиболее информативных публикаций, отражающих основные аспекты проблемы тестирования негенотоксичных канцерогенов.

Результаты

Результаты. В статье представлены проблема профилактики канцерогенеза, вызванного негенотоксическими соединениями, актуальность и научное обоснование необходимости тестирования этих соединений, обсуждены существующие подходы к разработке регламентированных мер контроля негенотоксических канцерогенов. Предложен авторский метод выявления эпигенетически активных соединений с помощью генно-модифицированных клеточных систем с репортёрным эпигенетически подавленным геном белка флуорофора в качестве интегрального скринингового теста на потенциальное влияние соединения на систему эпигенетической регуляции экспрессии генов.

Ограничения исследования

Ограничения исследования. Исследование основано на анализе открытых данных по тестированию генотоксических и негенотоксических соединений в вышеупомянутых базах данных.

Заключение

Заключение. Системно представлены данные, подтверждающие актуальность и необходимость тестирования негенотоксичных канцерогенов, существующие проблемы и способы решения задач в данной области профилактики заболеваемости злокачественными новообразованиями.

Соблюдение этических стандартов. Заключения комиссии по биоэтике не требуется.

Участие авторов

Участие авторов: Якубовская М.Г. – концепция и дизайн исследования, написание текста, редактирование, утверждение окончательного варианта статьи, ответственность за целостность всех частей статьи; Максимова В.П. – сбор и обработка материала, написание текста по тестированию эпигенетически активных соединений, редактирование; Белицкий Г.А. – написание текста, редактирование, утверждение окончательного варианта статьи; Кирсанов К.И. – концепция и дизайн исследования, редактирование, утверждение окончательного варианта статьи, ответственность за целостность всех частей статьи.

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, грант №25-15-00432.

Поступила в редакцию

Поступила в редакцию: 24 декабря 2025 / Поступила после исправления:12 января 2026 / Принята в печать: 02 февраля 2026 / Опубликована: 18 марта 2026

 

 

Introduction

Introduction. One of the reasons for the observed increase in the incidence of malignant neoplasms is the lack of control over the spread of non-genotoxic carcinogens. The purpose of this review is to analyze the problems in testing non-genotoxic carcinogens and ways to develop adequate approaches to their detection by analyzing the epigenetic activity of compounds.

Material and methods

Material and methods. The analysis of more than 200 scientific publications on the topic of detection of carcinogenic hazards has been carried out. The databases PubMed (149), Scopus (62), Web of Science (33), ResearchGate (15), RSCI (12) were used. Based on the analysis, 50 most informative publications reflecting the main aspects of the problem of testing non-genotoxic carcinogens have been selected.

Results

Results. The article presents the problem of preventing carcinogenesis caused by non-genotoxic compounds, the relevance and scientific justification for testing these compounds, and discusses existing approaches to developing regulated control measures for non-genotoxic carcinogens. An author’s method for detecting epigenetically active compounds using genetically modified cellular systems with a reporter epigenetically suppressed fluorophore protein gene is proposed as an integral screening test for the potential effect of a compound on the system of epigenetic regulation of gene expression.

Limitations

Limitations. The study is based on an analysis of open data on testing of genotoxic and non-genotoxic compounds in the aforementioned databases.

Conclusion

Conclusion. The data confirming the relevance and necessity of testing non-genotoxic carcinogens, existing challenges and ways to solve problems in the field of preventing the incidence of malignant neoplasms are systematically reviewed.

Compliance with ethical standards. The opinion of the Bioethics Commission is not required.

Authors’ contribution

Authors’ contribution: Yakubovskaya M.G. – concept and design of the study, writing, editing, approval of the final version of the article, responsibility for the integrity of all parts of the article; Maksimova V.P. – collection and processing of the material, writing the text for testing epigenetically active compounds, editing; Belitsky G.A. – writing the text, editing, approval of the final version; Kirsanov K.I. – research concept and design, editing, approval of the final version of the article, responsibility for the integrity of all parts of the article.

Conflict of interest

Conflict of interest. The authors declare that there are no obvious and potential conflicts of interest in connection with the publication of this article.

Funding

Funding. The research was supported by the Russian Science Foundation, grant No. 25-15-00432.

Received

Received: December 24, 2025 / Revised: January 12, 2026 / Accepted: February 2, 2026 / Published: March 18, 2026

 

 

профилактика заболеваемости злокачественными новообразованияминегенотоксичные канцерогеныхарактеристики канцерогенного агентаэпигенетическая активность химических соединенийрепортёрные тест-системыprevention of the incidence of malignant neoplasmsnon-genotoxic carcinogenscharacteristics of a carcinogenic agentepigenetic activity of chemical compoundsreporter test systemsReferencesКаприн А.Д., Старинский В.В., Шахзадова А.О. Злокачественные новообразования в России в 2019 году (заболеваемость и смертность). М.; 2020.Kaprin A.D., Starinskii V.V., Shakhzadova A.O. Malignant Neoplasms in Russia in 2024 (Incidence and Mortality) [Zlokachestvennye novoobrazovaniya v Rossii v 2019 godu (zabolevaemost’ i smertnost’)]. Moscow; 2025. (in Russian)Song M., Vogelstein B., Giovannucci E.L., Willett W.C., Tomasetti C. Cancer prevention: Molecular and epidemiologic consensus. Science. 2018; 361(6409): 1317–8. https://doi.org/10.1126/science.aau3830Song M., Vogelstein B., Giovannucci E.L., Willett W.C., Tomasetti C. Cancer prevention: Molecular and epidemiologic consensus. Science. 2018; 361(6409): 1317–8. https://doi.org/10.1126/science.aau3830Ильницкий А.П. 60 лет деятельности комиссии по канцерогенным факторам. Здравоохранение Российской Федерации. 2018; 62(3): 157–63. https://doi.org/10.18821/0044-197X-2018-62-3-157-163 https://elibrary.ru/uxqgthIlnitskiy A.P. The sixty years of functioning of the commission on carcinogenic factors. Zdravookhranenie Rossiiskoi Federatsii. 2018; 62(3): 157–63. https://doi.org/10.18821/0044-197X-2018-62-3-157-163 https://elibrary.ru/uxqgth (in Russian)Хабриев Р.У. Руководство по экспериментальному (доклиническому) изучению новых фармакологических веществ. М.: Медицина; 2005. https://elibrary.ru/qciiobKhabriev R.U. Guidelines for Experimental (Preclinical) Study of New Pharmacological Substances [Rukovodstvo po eksperimental’nomu (doklinicheskomu) izucheniyu novykh farmakologicheskikh veshchestv]. Moscow: Meditsina; 2005. https://elibrary.ru/qciiob (in Russian)Организация и проведение санитарно-гигиенической паспортизации канцерогеноопасных производств. Методические указания. М.; 1998.Organization and implementation of sanitary and hygienic certification of carcinogenic hazardous industries. Methodological guidelines. Moscow; 1998. (in Russian)Хамидулина Х.Х., Тарасова Е.В., Назаренко А.К., Тверская А.С., Дорофеева Е.В., Замкова И.В. и др. Особенности формирования доказательной базы при оценке и классификации опасности химических веществ по специфическим и отдалённым эффектам. Токсикологический вестник. 2025; 33(6): 502–12.Khamidulina Kh.Kh., Tarasova E.V., Nazarenko A.K., Tverskaya A.S., Dorofeeva E.V., Zamkova I.V., et al. Features of the evidence base formation for the assessment and classification of the hazards of chemicals based on specific and long-term effects. Toksikologicheskii vestnik. 2025; 33(6): 502–12. (in Russian)Белицкий Г.А., Кирсанов К.И., Лесовая Е.А., Максимова В.П., Соленова Л.Г., Якубовская М.Г. Химический канцерогенез и первичная профилактика рака. М.: АБВ-пресс; 2020.Belitskii G.A., Kirsanov K.I., Lesovaya E.A., Maksimova V.P., Solenova L.G., Yakubovskaya M.G. Chemical Carcinogenesis and Primary Cancer Prevention [Khimicheskii kantserogenez i pervichnaya profilaktika raka]. Moscow: ABV-press; 2020. (in Russian)Suarez-Torres J.D., Orozco C.A., Ciangherotti C.E. The 2-year rodent bioassay in drug and chemical carcinogenicity testing: Performance, utility, and configuration for cancer hazard identification. J. Pharmacol. Toxicol. Methods. 2021; 110: 107070. https://doi.org/10.1016/j.vascn.2021.107070Suarez-Torres J.D., Orozco C.A., Ciangherotti C.E. The 2-year rodent bioassay in drug and chemical carcinogenicity testing: Performance, utility, and configuration for cancer hazard identification. J. Pharmacol. Toxicol. Methods. 2021; 110: 107070. https://doi.org/10.1016/j.vascn.2021.107070Berenblum I. The cocarcinogenic action of croton resin. Cancer Res. 1941; 1: 44–50.Berenblum I. The cocarcinogenic action of croton resin. Cancer Res. 1941; 1: 44–50.Berenblum I. Cancer prevention as a realizable goal. Cancer. 1981; 47(10): 2346–8. https://doi.org/10.1002/1097-0142(19810515)47:10%3C2346::aid-cncr2820471004%3E3.0.co;2-xBerenblum I. Cancer prevention as a realizable goal. Cancer. 1981; 47(10): 2346–8. https://doi.org/10.1002/1097-0142(19810515)47:10%3C2346::aid-cncr2820471004%3E3.0.co;2-xKobets T., Iatropoulos M.J., Williams G.M. Mechanisms of DNA-reactive and epigenetic chemical carcinogens: applications to carcinogenicity testing and risk assessment. Toxicol. Res. (Camb.). 2019; 8(2): 123–45. https://doi.org/10.1039/c8tx00250aKobets T., Iatropoulos M.J., Williams G.M. Mechanisms of DNA-reactive and epigenetic chemical carcinogens: applications to carcinogenicity testing and risk assessment. Toxicol. Res. (Camb.). 2019; 8(2): 123–45. https://doi.org/10.1039/c8tx00250aШалгинских Н.А., Карпеченко Н.Ю., Оглоблина А.М., Лесовая Е.А., Кирсанов К.И., Набережнов Д.С., и др. Эпигенетические механизмы регуляции экспрессии генов в химическом канцерогенезе. Вопросы биологической, медицинской и фармацевтической химии. 2014; (3): 46–64. https://elibrary.ru/rydikrShalginskikh N.A., Karpechenko N.Yu., Ogloblina A.M., Lesovaya E.A., Kirsanov K.I., Naberezhnov D.S., et al. Epigenetic mechanisms of gene expression regulation in chemical carcinogenesis. Voprosy biologicheskoi, meditsinskoi i farmatsevticheskoi khimii. 2014; (3): 46–64. https://elibrary.ru/rydikr (in Russian)Ревазова Ю.А., Илюшина Н.А. К вопросу о негенотоксических канцерогенах. Токсикологический вестник. 2021; 29(4): 51–5. https://doi.org/10.36946/0869-7922-2021-29-4-51-55 https://elibrary.ru/hgulewRevazova Yu.A., Ilyushina N.A. On the issue of non-genotoxic carcinogens. Toksikologicheskii vestnik. 2021; 29(4): 51–5. https://doi.org/10.36946/0869-7922-2021-29-4-51-55 https://elibrary.ru/hgulew (in Russian)Desaulniers D., Vasseur P., Jacobs A., Aguila M.C., Ertych N., Jacobs M.N. Integration of epigenetic mechanisms into non-genotoxic carcinogenicity hazard assessment: focus on DNA methylation and histone modifications. Int. J. Mol. Sci. 2021; 22(20): 10969. https://doi.org/10.3390/ijms222010969Desaulniers D., Vasseur P., Jacobs A., Aguila M.C., Ertych N., Jacobs M.N. Integration of epigenetic mechanisms into non-genotoxic carcinogenicity hazard assessment: focus on DNA methylation and histone modifications. Int. J. Mol. Sci. 2021; 22(20): 10969. https://doi.org/10.3390/ijms222010969Veurink M., Koster M., Berg L.T. The history of DES, lessons to be learned. Pharm. World Sci. 2005; 27(3): 139–43. https://doi.org/10.1007/s11096-005-3663-zVeurink M., Koster M., Berg L.T. The history of DES, lessons to be learned. Pharm. World Sci. 2005; 27(3): 139–43. https://doi.org/10.1007/s11096-005-3663-zRodgers K.M., Udesky J.O., Rudel R.A., Brody J.G. Environmental chemicals and breast cancer: An updated review of epidemiological literature informed by biological mechanisms. Environ. Res. 2018; 160: 152–82. https://doi.org/10.1016/j.envres.2017.08.045Rodgers K.M., Udesky J.O., Rudel R.A., Brody J.G. Environmental chemicals and breast cancer: An updated review of epidemiological literature informed by biological mechanisms. Environ. Res. 2018; 160: 152–82. https://doi.org/10.1016/j.envres.2017.08.045Sahay D., Terry M.B., Miller R. Is breast cancer a result of epigenetic responses to traffic-related air pollution? A review of the latest evidence. Epigenomics. 2019; 11(6): 701–14. https://doi.org/10.2217/epi-2018-0158Sahay D., Terry M.B., Miller R. Is breast cancer a result of epigenetic responses to traffic-related air pollution? A review of the latest evidence. Epigenomics. 2019; 11(6): 701–14. https://doi.org/10.2217/epi-2018-0158Jacobs M.N., Colacci A., Corvi R., Vaccari M., Aguila M.C., Corvaro M., et al. Chemical carcinogen safety testing: OECD expert group international consensus on the development of an integrated approach for the testing and assessment of chemical non-genotoxic carcinogens. Arch. Toxicol. 2020; 94(8): 2899–23. https://doi.org/10.1007/s00204-020-02784-5Jacobs M.N., Colacci A., Corvi R., Vaccari M., Aguila M.C., Corvaro M., et al. Chemical carcinogen safety testing: OECD expert group international consensus on the development of an integrated approach for the testing and assessment of chemical non-genotoxic carcinogens. Arch. Toxicol. 2020; 94(8): 2899–23. https://doi.org/10.1007/s00204-020-02784-5Samet J.M., Chiu W.A., Cogliano V., Jinot J., Kriebel D., Lunn R.M., et al. The IARC monographs: updated procedures for modern and transparent evidence synthesis in cancer hazard identification. J. Natl Cancer Inst. 2020; 112(1): 30–7. https://doi.org/10.1093/jnci/djz169Samet J.M., Chiu W.A., Cogliano V., Jinot J., Kriebel D., Lunn R.M., et al. The IARC monographs: updated procedures for modern and transparent evidence synthesis in cancer hazard identification. J. Natl Cancer Inst. 2020; 112(1): 30–7. https://doi.org/10.1093/jnci/djz169Goodman S., Chappell G., Guyton K.Z., Pogribny I.P., Rusyn I. Epigenetic alterations induced by genotoxic occupational and environmental human chemical carcinogens: An update of a systematic literature review. Mutat. Res. Rev. Mutat. Res. 2022; 789: 108408. https://doi.org/10.1016/j.mrrev.2021.108408Goodman S., Chappell G., Guyton K.Z., Pogribny I.P., Rusyn I. Epigenetic alterations induced by genotoxic occupational and environmental human chemical carcinogens: An update of a systematic literature review. Mutat. Res. Rev. Mutat. Res. 2022; 789: 108408. https://doi.org/10.1016/j.mrrev.2021.108408Koltzoff N.K. Physiologie du de’velopment et genetique. Actualites scientifiques et Industrielles. Paris: Hermann et C-ie; 1935. (in French)Koltzoff N.K. Physiologie du de’velopment et genetique. Actualites scientifiques et Industrielles. Paris: Hermann et C-ie; 1935. (in French)Allis C.D., Jenuwein T. The molecular hallmarks of epigenetic control. Nat. Rev. Genet. 2016; 17(8): 487–500. https://doi.org/10.1038/nrg.2016.59Allis C.D., Jenuwein T. The molecular hallmarks of epigenetic control. Nat. Rev. Genet. 2016; 17(8): 487–500. https://doi.org/10.1038/nrg.2016.59Максимова В.П., Усалка О.Г., Макусь Ю.В., Попова В.Г., Трапезникова Е.С., Хайриева Г.И., и др. Нарушение метилирования ДНК при злокачественных новообразованиях. Успехи молекулярной онкологии. 2022; 9(4): 24–40. https://doi.org/10.17650/2313-805X-2022-9-4-24-40 https://elibrary.ru/scidnmMaksimova V.P., Usalka O.G., Makus Yu.V., Popova V.G., Trapeznikova E.S., Khayrieva G.I., et al. Aberrations of DNA methylation in Cancer. Uspekhi molekulyarnoi onkologii. 2022; 9(4): 24–40. https://doi.org/10.17650/2313-805X-2022-9-4-24-40 https://elibrary.ru/scidnm (in Russian)Slotkin R.K., Martienssen R. Transposable elements and the epigenetic regulation of the genome. Nat. Rev. Genet. 2007; 8(4): 272–85. https://doi.org/10.1038/nrg2072Slotkin R.K., Martienssen R. Transposable elements and the epigenetic regulation of the genome. Nat. Rev. Genet. 2007; 8(4): 272–85. https://doi.org/10.1038/nrg2072Misiak B., Ricceri L., Sasiadek M.M. Transposable elements and their epigenetic regulation in mental disorders: current evidence in the field. Front. Genet. 2019; 10: 580. https://doi.org/10.3389/fgene.2019.00580Misiak B., Ricceri L., Sasiadek M.M. Transposable elements and their epigenetic regulation in mental disorders: current evidence in the field. Front. Genet. 2019; 10: 580. https://doi.org/10.3389/fgene.2019.00580Prins G.S. Estrogen imprinting: when your epigenetic memories come back to haunt you. Endocrinology. 2008; 149(12): 5919–21. https://doi.org/10.1210/en.2008-1266Prins G.S. Estrogen imprinting: when your epigenetic memories come back to haunt you. Endocrinology. 2008; 149(12): 5919–21. https://doi.org/10.1210/en.2008-1266Stewart-Morgan K.R., Petryk N., Groth A. Chromatin replication and epigenetic cell memory. Nat. Cell Biol. 2020; 22(4): 361–71. https://doi.org/10.1038/s41556-020-0487-yStewart-Morgan K.R., Petryk N., Groth A. Chromatin replication and epigenetic cell memory. Nat. Cell Biol. 2020; 22(4): 361–71. https://doi.org/10.1038/s41556-020-0487-yPerera B.P.U., Svoboda L., Dolinoy D.C. Genomic tools for environmental epigenetics and implications for public health. Curr. Opin. Toxicol. 2019; 18: 27–33. https://doi.org/10.1016/j.cotox.2019.02.008Perera B.P.U., Svoboda L., Dolinoy D.C. Genomic tools for environmental epigenetics and implications for public health. Curr. Opin. Toxicol. 2019; 18: 27–33. https://doi.org/10.1016/j.cotox.2019.02.008Cavalli G., Heard E. Advances in epigenetics link genetics to the environment and disease. Nature. 2019; 571(7766): 489–99. https://doi.org/10.1038/s41586-019-1411-0Cavalli G., Heard E. Advances in epigenetics link genetics to the environment and disease. Nature. 2019; 571(7766): 489–99. https://doi.org/10.1038/s41586-019-1411-0Chung F.F., Herceg Z. The promises and challenges of toxico-epigenomics: environmental chemicals and their impacts on the epigenome. Environ. Health Perspect. 2020; 128(1): 15001. https://doi.org/10.1289/ehp6104Chung F.F., Herceg Z. The promises and challenges of toxico-epigenomics: environmental chemicals and their impacts on the epigenome. Environ. Health Perspect. 2020; 128(1): 15001. https://doi.org/10.1289/ehp6104Marczylo E.L., Jacobs M.N., Gant T.W. Environmentally induced epigenetic toxicity: potential public health concerns. Crit. Rev. Toxicol. 2016; 46(8): 676–700. https://doi.org/10.1080/10408444.2016.1175417Marczylo E.L., Jacobs M.N., Gant T.W. Environmentally induced epigenetic toxicity: potential public health concerns. Crit. Rev. Toxicol. 2016; 46(8): 676–700. https://doi.org/10.1080/10408444.2016.1175417Bijlsma N., Cohen M.M. Environmental chemical assessment in clinical practice: unveiling the elephant in the room. Int. J. Environ. Res. Public Health. 2016; 13(2): 181. https://doi.org/10.3390/ijerph13020181Bijlsma N., Cohen M.M. Environmental chemical assessment in clinical practice: unveiling the elephant in the room. Int. J. Environ. Res. Public Health. 2016; 13(2): 181. https://doi.org/10.3390/ijerph13020181Wang T., Pehrsson E.C., Purushotham D., Li D., Zhuo X., Zhang B., et al. The NIEHS TaRGET II Consortium and environmental epigenomics. Nat. Biotechnol. 2018; 36(3): 225–7. https://doi.org/10.1038/nbt.4099Wang T., Pehrsson E.C., Purushotham D., Li D., Zhuo X., Zhang B., et al. The NIEHS TaRGET II Consortium and environmental epigenomics. Nat. Biotechnol. 2018; 36(3): 225–7. https://doi.org/10.1038/nbt.4099Moreno F.S., Heidor R., Pogribny I.P. Nutritional epigenetics and the prevention of hepatocellular carcinoma with bioactive food constituents. Nutr. Cancer. 2016; 68(5): 719–33. https://doi.org/10.1080/01635581.2016.1180410Moreno F.S., Heidor R., Pogribny I.P. Nutritional epigenetics and the prevention of hepatocellular carcinoma with bioactive food constituents. Nutr. Cancer. 2016; 68(5): 719–33. https://doi.org/10.1080/01635581.2016.1180410Angrish M.M., Allard P., McCullough S.D., Druwe I.L., Chadwick L., Hines E., et al. Epigenetic applications in adverse outcome pathways and environmental risk evaluation. Environ. Health Perspect. 2018; 126(4): 045001. https://doi.org/10.1289/ehp2322Angrish M.M., Allard P., McCullough S.D., Druwe I.L., Chadwick L., Hines E., et al. Epigenetic applications in adverse outcome pathways and environmental risk evaluation. Environ. Health Perspect. 2018; 126(4): 045001. https://doi.org/10.1289/ehp2322Cote I.L., McCullough S.D., Hines R.N., Vandenberg J.J. Application of epigenetic data in human health risk assessment. Curr. Opin. Toxicol. 2017; 6: 71–8. https://doi.org/10.1016/j.cotox.2017.09.002Cote I.L., McCullough S.D., Hines R.N., Vandenberg J.J. Application of epigenetic data in human health risk assessment. Curr. Opin. Toxicol. 2017; 6: 71–8. https://doi.org/10.1016/j.cotox.2017.09.002Chen Z., Liu Y., Wright F.A., Chiu W.A., Rusyn I. Rapid hazard characterization of environmental chemicals using a compendium of human cell lines from different organs. ALTEX. 2020; 37(4): 623–38. https://doi.org/10.14573/altex.2002291Chen Z., Liu Y., Wright F.A., Chiu W.A., Rusyn I. Rapid hazard characterization of environmental chemicals using a compendium of human cell lines from different organs. ALTEX. 2020; 37(4): 623–38. https://doi.org/10.14573/altex.2002291Herceg Z., Lambert M.P., van Veldhoven K., Demetriou C., Vineis P., Smith M.T., et al. Towards incorporating epigenetic mechanisms into carcinogen identification and evaluation. Carcinogenesis. 2013; 34(9): 1955–67. https://doi.org/10.1093/carcin/bgt212Herceg Z., Lambert M.P., van Veldhoven K., Demetriou C., Vineis P., Smith M.T., et al. Towards incorporating epigenetic mechanisms into carcinogen identification and evaluation. Carcinogenesis. 2013; 34(9): 1955–67. https://doi.org/10.1093/carcin/bgt212Bonasio R. The expanding epigenetic landscape of non-model organisms. J. Exp. Biol. 2015; 218(Pt. 1): 114–22. https://doi.org/10.1242/jeb.110809Bonasio R. The expanding epigenetic landscape of non-model organisms. J. Exp. Biol. 2015; 218(Pt. 1): 114–22. https://doi.org/10.1242/jeb.110809Dolinoy D.C. The agouti mouse model: an epigenetic biosensor for nutritional and environmental alterations on the fetal epigenome. Nutr. Rev. 2008; 66(Suppl. l): S7–11. https://doi.org/10.1111/j.1753-4887.2008.00056.xDolinoy D.C. The agouti mouse model: an epigenetic biosensor for nutritional and environmental alterations on the fetal epigenome. Nutr. Rev. 2008; 66(Suppl. l): S7–11. https://doi.org/10.1111/j.1753-4887.2008.00056.xParfett C.L., Desaulniers D. A Tox21 approach to altered epigenetic landscapes: assessing epigenetic toxicity pathways leading to altered gene expression and oncogenic transformation in vitro. Int. J. Mol. Sci. 2017; 18(6): 1179. https://doi.org/10.3390/ijms18061179Parfett C.L., Desaulniers D. A Tox21 approach to altered epigenetic landscapes: assessing epigenetic toxicity pathways leading to altered gene expression and oncogenic transformation in vitro. Int. J. Mol. Sci. 2017; 18(6): 1179. https://doi.org/10.3390/ijms18061179Yoshida W., Baba Y., Karube I. Global DNA methylation detection system using MBD-fused luciferase based on bioluminescence resonance energy transfer assay. Anal. Chem. 2016; 88(18): 9264–8. https://doi.org/10.1021/acs.analchem.6b02565Yoshida W., Baba Y., Karube I. Global DNA methylation detection system using MBD-fused luciferase based on bioluminescence resonance energy transfer assay. Anal. Chem. 2016; 88(18): 9264–8. https://doi.org/10.1021/acs.analchem.6b02565Han W., Shi M., Spivack S.D. Site-specific methylated reporter constructs for functional analysis of DNA methylation. Epigenetics. 2013; 8(11): 1176–87. https://doi.org/10.4161/epi.26195Han W., Shi M., Spivack S.D. Site-specific methylated reporter constructs for functional analysis of DNA methylation. Epigenetics. 2013; 8(11): 1176–87. https://doi.org/10.4161/epi.26195Campa C.C., Weisbach N.R., Santinha A.J., Incarnato D., Platt R.J. Multiplexed genome engineering by Cas12a and CRISPR arrays encoded on single transcripts. Nat. Methods. 2019; 16(9): 887–93. https://doi.org/10.1038/s41592-019-0508-6Campa C.C., Weisbach N.R., Santinha A.J., Incarnato D., Platt R.J. Multiplexed genome engineering by Cas12a and CRISPR arrays encoded on single transcripts. Nat. Methods. 2019; 16(9): 887–93. https://doi.org/10.1038/s41592-019-0508-6Ding X., Seebeck T., Feng Y., Jiang Y., Davis G.D., Chen F. Improving CRISPR-Cas9 genome editing efficiency by fusion with chromatin-modulating peptides. CRISPR J. 2019; 2: 51–63. https://doi.org/10.1089/crispr.2018.0036Ding X., Seebeck T., Feng Y., Jiang Y., Davis G.D., Chen F. Improving CRISPR-Cas9 genome editing efficiency by fusion with chromatin-modulating peptides. CRISPR J. 2019; 2: 51–63. https://doi.org/10.1089/crispr.2018.0036Martinez E.D., Dull A.B., Beutler J.A., Hager G.L. High-content fluorescence‐based screening for epigenetic modulators. Methods Enzymol. 2006; 414: 21–36. https://doi.org/10.1016/s0076-6879(06)14002-1Martinez E.D., Dull A.B., Beutler J.A., Hager G.L. High-content fluorescence‐based screening for epigenetic modulators. Methods Enzymol. 2006; 414: 21–36. https://doi.org/10.1016/s0076-6879(06)14002-1Poleshko A., Einarson M.B., Shalginskikh N., Zhang R., Adams P.D., Skalka A.M., et al. Identification of a functional network of human epigenetic silencing factors. J. Biol. Chem. 2010; 285(1): 422–33. https://doi.org/10.1074/jbc.m109.064667Poleshko A., Einarson M.B., Shalginskikh N., Zhang R., Adams P.D., Skalka A.M., et al. Identification of a functional network of human epigenetic silencing factors. J. Biol. Chem. 2010; 285(1): 422–33. https://doi.org/10.1074/jbc.m109.064667Poleshko A., Palagin I., Zhang R., Boimel P. Identification of cellular proteins that maintain retroviral epigenetic silencing: evidence for an antiviral response. J. Virol. 2008; 82(5): 2313–23. https://doi.org/10.1128/jvi.01882-07Poleshko A., Palagin I., Zhang R., Boimel P. Identification of cellular proteins that maintain retroviral epigenetic silencing: evidence for an antiviral response. J. Virol. 2008; 82(5): 2313–23. https://doi.org/10.1128/jvi.01882-07Maksimova V., Shalginskikh N., Vlasova O., Usalka O., Beizer A., Bugaeva P., et al. HeLa TI cell-based assay as a new approach to screen for chemicals able to reactivate the expression of epigenetically silenced genes. PloS One. 2021; 16(6): e0252504. https://doi.org/10.1371/journal.pone.0252504Maksimova V., Shalginskikh N., Vlasova O., Usalka O., Beizer A., Bugaeva P., et al. HeLa TI cell-based assay as a new approach to screen for chemicals able to reactivate the expression of epigenetically silenced genes. PloS One. 2021; 16(6): e0252504. https://doi.org/10.1371/journal.pone.0252504Oku Y., Madia F., Lau P., Paparella M., McGovern T., Luijten M., et al. Analyses of transcriptomics cell signalling for pre-screening applications in the integrated approach for testing and assessment of non-genotoxic carcinogens. Int. J. Mol. Sci. 2022; 23(21): 12718. https://doi.org/10.3390/ijms232112718Oku Y., Madia F., Lau P., Paparella M., McGovern T., Luijten M., et al. Analyses of transcriptomics cell signalling for pre-screening applications in the integrated approach for testing and assessment of non-genotoxic carcinogens. Int. J. Mol. Sci. 2022; 23(21): 12718. https://doi.org/10.3390/ijms232112718

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