oncotomskСибирский онкологический журналSiberian journal of oncology1814-48612312-3168Tomsk National Research Medical Сепtеr of the Russian Academy of Sciences10.21294/1814-4861-2023-22-5-145-160oncotomsk-2768Research ArticleОБЗОРЫREVIEWSЭндокринные дизрапторы в канцерогенном фоне биосферыEndocrine disruptors as promoters of biosphere carcinogenic backgroundБелицкийГ. А.BelitskyG. A.

Белицкий Геннадий Альтерович, доктор медицинских наук, профессор, ведущий научный сотрудник отдела химического канцерогенеза.

115478, Москва, Каширское шоссе, 24

Gennady A. Belitsky - MD, DSc, Professor, Leading Researcher, Department of Chemical Carcinogenesis.

24, Kashirskoye shosse, Moscow, 115522

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

Кирсанов Кирилл Игоревич - доктор биологических наук, заведующий лабораторией канцерогенных веществ отдела химического канцерогенеза.

115478, Москва, Каширское шоссе, 24

Kirill I. Kirsanov - DSc, Head of Laboratory of Carcinogenic Substances, Department of Chemical Carcinogenesis.

24, Kashirskoye shosse, Moscow, 115522

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

Лесовая Екатерина Андреевна - доктор биологических наук, старший научный сотрудник отдела химического канцерогенеза, Researcher ID (WOS): J-7790-2015.

115478, Москва, Каширское шоссе, 24

Ekaterina A. Lesovaya - DSc, Senior Researcher, Department of Chemical Carcinogenesis. Researcher ID (WOS): J-7790-2015.

24, Kashirskoye shosse, Moscow, 115522

https://orcid.org/0000-0003-3318-9391ЖидковаЕ. М.ZhidkovaE. M.

Жидкова Екатерина Михайловна - младший научный сотрудник отдела химического канцерогенеза.

115478, Москва, Каширское шоссе, 24

Ekaterina M. Zhidkova - Junior Researcher, Department of Chemical Carcinogenesis, Author ID (Scopus): 57195322730.

24, Kashirskoye shosse, Moscow, 115522

ХитровоИ. А.KhitrovoI. A.

Хитрово Ирина Александровна - кандидат химических наук, старший научный сотрудник лаборатории механизмов химического канцерогенеза. Author ID (Scopus): 6701477868.

115478, Москва, Каширское шоссе, 24

Irina A. Khitrovo - PhD, Senior Researcher, Laboratory of Mechanisms of Chemical Carcinogenesis, Author ID (Scopus): 6701477868.

24, Kashirskoye shosse, Moscow, 115522

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

Якубовская Марианна Геннадиевна - доктор медицинских наук, заведующая отделом химического канцерогенеза, Researcher ID (WOS): R-6984-2016.

115478, Москва, Каширское шоссе, 24

Marianna G. Yakubovskaya - MD, DSc, Head of the Department of Chemical Carcinogenesis, Researcher ID (WOS): R-6984-2016.

24, Kashirskoye shosse, Moscow, 115522

mgyakubovskaya@mail.ruФГБУ «Национальный медицинский исследовательский центр онкологии им. Н.Н. Блохина» Минздрава РоссииРоссияN.N. Blokhin National medical Research center of oncology of the Ministry of Health of the RussiaRussian Federation202316112023225145160Copyright © Белицкий Г.А., Кирсанов К.И., Лесовая Е.А., Жидкова Е.М., Хитрово И.А., Якубовская М.Г., 20232023Белицкий Г.А., Кирсанов К.И., Лесовая Е.А., Жидкова Е.М., Хитрово И.А., Якубовская М.Г.Belitsky G.A., Kirsanov K.I., Lesovaya E.A., Zhidkova E.M., Khitrovo I.A., Yakubovskaya M.G.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.siboncoj.ru/jour/article/view/2768

Цель исследования – представить современную концепцию по влиянию эндокринных дизрапторов, вносящих существенный вклад в общий уровень загрязнения биосферы антропогенными ксенобиотиками, на процесс канцерогенеза.

Материал и методы

Материал и методы. При подготовке обзора были проанализированы статьи по изучению эффектов эндокринных дизрапторов, имеющиеся в информационных базах биомедицинской литературы sciVerse scopus, pubmed, Web of science, РИНЦ. В обзоре процитированы 65 современных публикаций, из которых 21 работа была опубликована в течение трех последних лет, 3 статьи представляют собой официальные документы по рискам, сопряженным с использованием эндокринных дизрапторов, а 10 статей относятся к публикациям, создающим предпосылки для выделения данных соединений в отдельную функциональную группу.

Результаты

Результаты. Наиболее изучена роль эндокринных дизрапторов в возникновении злокачественных новообразований репродуктивных органов. Данные соединения в качестве агонистов или антагонистов нарушают гормональный баланс организма, синтез естественных гормонов, их секрецию, транспорт, метаболизм, связывание и деградацию. Кроме того, они стимулируют альтернативные пути пролиферации, активируя рецепторы, сопряженные с g-белком, эстроген-связанный рецептор eRRγ, β-адреновые рецепторы и ряд других. Одним из основных механизмов действия эндокринных дизрапторов является влияние на эпигенетическую регуляцию экспрессии генов, а именно, на метилирование/деметилирование cpg островков ДНК, модификацию гистонов и экспрессию некодирующих РНК. Эффекты ряда эндокринных дизрапторов могут не иметь линейной зависимости от дозы и времени экспозиции и могут быть вызваны концентрациями, соответствующими их реальному содержанию в биосфере и обнаруживаемыми в крови пуповины и женском молоке. Кроме того, активируя изоформы цитохрома Р450, они способствуют метаболической активации проканцерогенных соединений, которые в смеси с ними загрязняют биосферу. При этом эндокринные дизрапторы повышают риск развития злокачественных новообразований гормон-зависимых органов как при непосредственной экспозиции организма, так и в результате трансплацентарного воздействия.

Заключение

Заключение. Эндокринные дизрапторы, относящиеся к негенотоксичным канцерогенам, являются распространенными загрязнениями окружающей среды. Нарушая гормональную регуляцию дифференцировки и функционирования гормон-продуцирующих и гормон-респонсивных клеток, эти соединения могут индуцировать/промотировать процессы канцерогенеза.

The main aim of the study is to analyze modern knowledge on endocrine disruptors, non-genotoxic carcinogens, contributing significantly to the total level of contamination of the biosphere by anthropogenic blastomogens.

Material and Methods

Material and Methods. For the review preparation, we analyzed articles on molecular mechanisms of the effects of endocrine disruptors, available at biomedical literature databases sciVerse scopus, pubmed, Web of science, Rsci. The review cited 65 recent publications, 21 of them being published over the past three years, 3 papers being the official documents on hazards associated with the use of endocrine disruptors, and 10 papers presenting a background to separate endocrine disruptors into the group of compounds with specific functional activity.

Results

Results. The role of endocrine disruptors involves the development of the tumors of reproductive organs. They may reveal the properties of strong agonists or antagonists disrupting the hormonal balance by inhibition of the synthesis of natural hormones, their secretion, transport, metabolism, binding or degradation. In addition, they activate alternative proliferation signaling pathways by activating g-proteincoupled receptors, estrogen-bound eRRγ or/and β-adrenergic receptors. The main mechanism of action of endocrine disruptors is the induction of epigenetic modifications, in particular, methylation/demethylation of cpg dNa islands, histone modifications and changes in expression of non-coding RNa. since the effects of endocrine disruptors are nonlinear, they can be caused by concentrations corresponding to the real content in the biosphere and detected in the umbilical blood and breast milk. In addition, they contribute to the metabolic activation of the procarcinogens, the main component of air pollution, by activation of the cytochrome p450 isoforms.

Conclusion

Conclusion. Endocrine disruptors can underlie the development of tumors of hormone-dependent organs both at direct and transplacental exposure.

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