toxreviewТоксикологический вестникToxicological Review0869-79223034-4611Federal Scientific Center of Hygiene named after F.F. Erisman10.36946/0869-7922-2018-1-2-7toxreview-103Research ArticleСтатьиЭПИГЕНЕТИЧЕСКАЯ ТОКСИКОЛОГИЯ: ПЕРСПЕКТИВЫ РАЗВИТИЯEPEGENTIC TOXICOLOGY: PERSPECTIVES OF THE DEVELOPMENTСофроновГ. А.SofronovG. A.noemail@neicon.ruПаткинЕ. Л.PatkinE. L.noemail@neicon.ruФГБНУ Институт экспериментальной медициныРоссияInstitute of Experimental MedicineRussian Federation2018280220180127Copyright © Софронов Г.А., Паткин Е.Л., 20182018Софронов Г.А., Паткин Е.Л.Sofronov G.A., Patkin E.L.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.toxreview.ru/jour/article/view/103

Одной из сложных проблем современной экспериментальной токсикологии остаются молекулярные механизмы формирования нарушений здоровья людей в отдаленные сроки после острого либо хронического воздействия токсичных химических загрязнителей окружающей среды (экотоксикантов). Выявление и понимание того, какие эпигенетические изменения индуцируются окружающей средой, и как они могут приводить к неблагоприятным результатам, имеет жизненно важное значение для охраны здоровья населения. Поэтому мы рассматриваем современное понимание эпигенетических механизмов, участвующих в жизненном цикле млекопитающих, и оцениваем имеющиеся данные относительно экологически обусловленной эпигенетической токсичности, а соответственно, формирующейся эпигенетической (эпигеномной) регуляторной токсикологии.

One of the complex problems of modern experimental toxicology remains the molecular mechanism of formation of human health disorders separated at different time periods from acute or chronic exposure to toxic environmental pollutants (ecotoxicants). Identifying and understanding what epigenetic changes are induced by the environment, and how they can lead to unfavorable outcome, are vital for protecting public health. Therefore, we consider it important a modern understanding of epigenetic mechanisms involved in the life cycle of mammals and assess available data on the environmentally caused epigenetic toxicity and, accordingly fledging epigenenomic (epigenetic) regulatory toxicology.

эпигенетикаэпигеномикаэпигенетические механизмытоксикоэпигенетикаэпигенетические изменения в раннем развитииметилирование ДНКбисфенол Ахлористый кадмийклеточные культуры человекахромосомыхроматинмежпоколенческое наследование эпигенома после воздействия токсикантамиepigeneticsepigenomicsepigenetic mechanismstoxicoepigeneticsepigenetic changes in early developmentDNA methylationbisphenol Acadmium chloridehuman cell cultureschromosomeschromatinintergenerational inheritance of epigenome after exposure to toxicantsReferencesEgger G., Liang G., Aparicio A., Jones P. A. Epigenetics in human disease and prospects for epigenetic therapy. Nature. 2004; 429: 457-463.Egger G., Liang G., Aparicio A., Jones P. A. Epigenetics in human disease and prospects for epigenetic therapy. Nature. 2004; 429: 457-463.Bernal A. J., Jirtle R. L. Epigenomic disruption: the effects of early developmental exposures. Birth Defects Res. A Clin. Mol. Teratol. 2010; 88: 938- 944.Bernal A. J., Jirtle R. L. Epigenomic disruption: the effects of early developmental exposures. Birth Defects Res. A Clin. Mol. Teratol. 2010; 88: 938- 944.Medvedeva Y. A., Khamis A. M., Kulakovskiy I. V., Ba-Alawi W., Bhuyan M. S., Kawaji H., Lassmann T., Harbers M., Forrest A. R., Bajic, V. B. Effects of cytosine methylation on transcription factor binding sites. BMC Genomics. 2014; 119: 10.1186/1471-2164-15-119.Medvedeva Y. A., Khamis A. M., Kulakovskiy I. V., Ba-Alawi W., Bhuyan M. S., Kawaji H., Lassmann T., Harbers M., Forrest A. R., Bajic, V. B. Effects of cytosine methylation on transcription factor binding sites. BMC Genomics. 2014; 119: 10.1186/1471-2164-15-119.Hackett J. A., Surani M.A. DNA methylation dynamics during the mammalian life cycle. Philos Trans R Soc Lond. B,Biol Sci. 2013; 368 : 20110328.Hackett J. A., Surani M.A. DNA methylation dynamics during the mammalian life cycle. Philos Trans R Soc Lond. B,Biol Sci. 2013; 368 : 20110328.Messerschmidt D.M. A twist in zygotic reprogramming. Nat. Cell Biol. 2016; 18:139–140.Messerschmidt D.M. A twist in zygotic reprogramming. Nat. Cell Biol. 2016; 18:139–140.Li E., Bestor T.H., Jaenisch R. Targeted mutation of the DNA methyltransferase gene results in embryonic lethality. Cell. 1992; 69 : 915–926.Li E., Bestor T.H., Jaenisch R. Targeted mutation of the DNA methyltransferase gene results in embryonic lethality. Cell. 1992; 69 : 915–926.Okano M, Bell D.W, Haber D.A, Li E. DNA methyltransferases Dnmt3a and Dnmt3b are essential for de novo methylation and mammalian development. Cell. 1999; 99:247–257.Okano M, Bell D.W, Haber D.A, Li E. DNA methyltransferases Dnmt3a and Dnmt3b are essential for de novo methylation and mammalian development. Cell. 1999; 99:247–257.Gowher H., Liebert K., Hermann A., Xu G., Jeltsch A.Mechanism of stimulation of catalytic activity of Dnmt3A and Dnmt3B DNA-(cytosine-C5)-methyltransferases by Dnmt3L.Gowher H., Liebert K., Hermann A., Xu G., Jeltsch A.Mechanism of stimulation of catalytic activity of Dnmt3A and Dnmt3B DNA-(cytosine-C5)-methyltransferases by Dnmt3L.J. Biol. Chem. 2005; 280:13341– 13348.J. Biol. Chem. 2005; 280:13341– 13348.Tahiliani M., Koh K.P., Shen Y., Pastor W.A., Bandukwala H., et al. Conversion of 5-methylcytosine to 5-hydroxymethylcytosine in mammalian DNA by MLL partner TETScience. 2009; 324:930–935.Tahiliani M., Koh K.P., Shen Y., Pastor W.A., Bandukwala H., et al. Conversion of 5-methylcytosine to 5-hydroxymethylcytosine in mammalian DNA by MLL partner TETScience. 2009; 324:930–935.Ito S., Shen L., Dai Q., Wu S.C., Collins L.B., Swenberg J.A., He C., Zhang Y.. Tet proteins can convert 5-methylcytosine to 5-formylcytosine and 5-carboxylcytosine. Science. 2011; 333:1300–1303.Ito S., Shen L., Dai Q., Wu S.C., Collins L.B., Swenberg J.A., He C., Zhang Y.. Tet proteins can convert 5-methylcytosine to 5-formylcytosine and 5-carboxylcytosine. Science. 2011; 333:1300–1303.Dean W. DNA methylation and demethylation: a pathway to gametogenesis and development. Mol. Reprod. Dev. 2014; 81:113–125.Dean W. DNA methylation and demethylation: a pathway to gametogenesis and development. Mol. Reprod. Dev. 2014; 81:113–125.Kornberg R.D, Lorch Y. Twenty-five years of the nucleosome,fundamental particle of the eukaryote chromosome. Cell. 1999; 98:285–294.Kornberg R.D, Lorch Y. Twenty-five years of the nucleosome,fundamental particle of the eukaryote chromosome. Cell. 1999; 98:285–294.Strahl B.D, Allis C.D. 20The language of covalent histone modifications. Nature. 403:41–45.,Strahl B.D, Allis C.D. 20The language of covalent histone modifications. Nature. 403:41–45.,Khare S.P., Habib F., Sharma R., Gadewal N., Gupta S., Galande S. Histome-a relational knowledgebase of human histone proteins and histone modifying enzymes. Nucleic Acids Res. 2012; 40 : D337–D342.Khare S.P., Habib F., Sharma R., Gadewal N., Gupta S., Galande S. Histome-a relational knowledgebase of human histone proteins and histone modifying enzymes. Nucleic Acids Res. 2012; 40 : D337–D342.Mattick J.S. A new paradigm for developmental biology. J Exp. Biol. 2007; 210:1526–1547.Mattick J.S. A new paradigm for developmental biology. J Exp. Biol. 2007; 210:1526–1547.Cook M.S., Blelloch R.. Small RNAs in germline development. Curr. Top. Dev. Biol. 2013; 102:159–205.Cook M.S., Blelloch R.. Small RNAs in germline development. Curr. Top. Dev. Biol. 2013; 102:159–205.Beaujean N. Histone post-translational modifications in preimplantation mouse embryos and their role in nuclear architecture. Mol. Reprod. Dev. 2014; 81:100–112.Beaujean N. Histone post-translational modifications in preimplantation mouse embryos and their role in nuclear architecture. Mol. Reprod. Dev. 2014; 81:100–112.Luk A.C., Chan W.Y., Rennert O.M., Lee T.L. Long noncoding RNAs in spermatogenesis: insights from recent high-throughput transcriptome studies. Reproduction. 2014; 147:R131–R141.Luk A.C., Chan W.Y., Rennert O.M., Lee T.L. Long noncoding RNAs in spermatogenesis: insights from recent high-throughput transcriptome studies. Reproduction. 2014; 147:R131–R141.Marcho C., Cui W., Mager J. Epigenetic dynamics during preimplantation development. Reproduction. 2015; 150:R109–R120.Marcho C., Cui W., Mager J. Epigenetic dynamics during preimplantation development. Reproduction. 2015; 150:R109–R120.Bateson P., Barker D., Clutton-Brock T., Deb D., et al. (). Developmental plasticity and human health. Nature. 2004; 430(6998): 419-421.Bateson P., Barker D., Clutton-Brock T., Deb D., et al. (). Developmental plasticity and human health. Nature. 2004; 430(6998): 419-421.Heindel J. J., Balbus J., Birnbaum L., Brune-Drisse M. N., et al. Developmental Origins of Health and Disease: Integrating Environmental Influences. Endocrinology. 2015; 156:3416-34Heindel J. J., Balbus J., Birnbaum L., Brune-Drisse M. N., et al. Developmental Origins of Health and Disease: Integrating Environmental Influences. Endocrinology. 2015; 156:3416-34Waterland R. A., Michels K. B. Epigenetic epidemiology of the developmental origins hypothesis. Annu. Rev. Nutr. 2007; 27: 363-388.Waterland R. A., Michels K. B. Epigenetic epidemiology of the developmental origins hypothesis. Annu. Rev. Nutr. 2007; 27: 363-388.Zambrano E., Martinez-Samayoa P.M., Bautista CJ, Deas M., et al. Sex differences in transgenerational alterations of growth and metabolism in progeny (F2) of female offspring (F1) of rats fed a low protein diet during pregnancy and lactation. Jю Physiolю 2005; 566:225–236.Zambrano E., Martinez-Samayoa P.M., Bautista CJ, Deas M., et al. Sex differences in transgenerational alterations of growth and metabolism in progeny (F2) of female offspring (F1) of rats fed a low protein diet during pregnancy and lactation. Jю Physiolю 2005; 566:225–236.Daxinger L., Whitelaw E. Understanding transgenerational epigenetic inheritance via the gametes in mammals. Nat Rev Genet 2012; 13:153–162;Daxinger L., Whitelaw E. Understanding transgenerational epigenetic inheritance via the gametes in mammals. Nat Rev Genet 2012; 13:153–162;Skinner M.K. What is an epigenetic transgenerational phenotype? F3 or FReprod. Toxicol. 2008; 25:2–6.Skinner M.K. What is an epigenetic transgenerational phenotype? F3 or FReprod. Toxicol. 2008; 25:2–6.Jirtle R.L., Skinner M.K. Environmental epigenomics and disease susceptibility. Nat Rev Genet 2007;8:253–262.Jirtle R.L., Skinner M.K. Environmental epigenomics and disease susceptibility. Nat Rev Genet 2007;8:253–262.Sharma A. Transgenerational epigenetic inheritance: focus on soma to germline information transfer. Prog. Biophys. Mol. Biol. 2013; 113:439–446.Sharma A. Transgenerational epigenetic inheritance: focus on soma to germline information transfer. Prog. Biophys. Mol. Biol. 2013; 113:439–446.Perera F., Herbstman J. Prenatal environmental exposures,epigenetics, and disease. Reprod. Toxicol. 2011;31:363–73Perera F., Herbstman J. Prenatal environmental exposures,epigenetics, and disease. Reprod. Toxicol. 2011;31:363–73Нониашвили Е.М., Софронов Г.А., Паткин Е.Л. Влияние малых доз бисфенола А на доимплантационное развитие зародышей мышей in vitro.Акад. Журнал Западной Сибири. 2013; 9: 100- 10129 / Noniashvili E.M., Sofronov G.A., Patkin E.L. The influence of low dose bisphenol A on preimplanataion development of mice in vitro. The Acad. J. of West Siberia. 2013; 9: 100- 101 (in Russian)Нониашвили Е.М., Софронов Г.А., Паткин Е.Л. Влияние малых доз бисфенола А на доимплантационное развитие зародышей мышей in vitro.Акад. Журнал Западной Сибири. 2013; 9: 100- 10129 / Noniashvili E.M., Sofronov G.A., Patkin E.L. The influence of low dose bisphenol A on preimplanataion development of mice in vitro. The Acad. J. of West Siberia. 2013; 9: 100- 101 (in Russian)Паткин Е.Л., Софронов Г.А. Эпигенетические и эпигеномные механизмы возникновения и наследования эколого-зависимых нарушений здоровья человека. “Перспективные направления развития науки в Петербурге”, Санкт-Петербургский научный центр РАН, СПб., 2015, с. 320 – 3/ Patkin E.L., Sofronov G.A. Epigenetic and Epigenomic mechanisms of origin and inheritance of ecology dependent humant health disorders. “Perspectives od science development in Petersburg”. S-Ptersburg RAN scientific centre, Spb., 2015, 320-330 (in Russian).Паткин Е.Л., Софронов Г.А. Эпигенетические и эпигеномные механизмы возникновения и наследования эколого-зависимых нарушений здоровья человека. “Перспективные направления развития науки в Петербурге”, Санкт-Петербургский научный центр РАН, СПб., 2015, с. 320 – 3/ Patkin E.L., Sofronov G.A. Epigenetic and Epigenomic mechanisms of origin and inheritance of ecology dependent humant health disorders. “Perspectives od science development in Petersburg”. S-Ptersburg RAN scientific centre, Spb., 2015, 320-330 (in Russian).Паткин Е.Л., Софронов Г.А. Эколого – зависимые заболевания человека. Эпигенетические механизмы возникновения и наследования. Медицинский академический журнал. 2015; 15: 7-/ Patkin E.L., Sofronov G.A. Ecodependent human diseases. Epigenetical mechanisms of origin and inheritance. Medic. Acad. J. 2015; 15: 7-(in Russian).Паткин Е.Л., Софронов Г.А. Эколого – зависимые заболевания человека. Эпигенетические механизмы возникновения и наследования. Медицинский академический журнал. 2015; 15: 7-/ Patkin E.L., Sofronov G.A. Ecodependent human diseases. Epigenetical mechanisms of origin and inheritance. Medic. Acad. J. 2015; 15: 7-(in Russian).Reik W., Dean W., Walter J. Epigenetic reprogramming in mammalian development. Science. 2001; 293:1089- 1093.Reik W., Dean W., Walter J. Epigenetic reprogramming in mammalian development. Science. 2001; 293:1089- 1093.Smallwood S. A., Kelsey G. De novo DNA methylation: a germ cell perspective. Trends Genet. 2012; 28: 33-Smallwood S. A., Kelsey G. De novo DNA methylation: a germ cell perspective. Trends Genet. 2012; 28: 33-Messerschmidt D. M., Knowles B. B., Solter D. (). DNA methylation dynamics during epigenetic reprogramming in the germline and preimplantation embryos. Genes Dev. 2014; 28: 812-828.Messerschmidt D. M., Knowles B. B., Solter D. (). DNA methylation dynamics during epigenetic reprogramming in the germline and preimplantation embryos. Genes Dev. 2014; 28: 812-828.Anderson O. S., Sant K. E., Dolinoy D. C. Nutrition and epigenetics: an 2014interplay of dietary methyl donors, one-carbon metabolism and DNA methylation. J. Nutr. Biochem. 2012; 23: 853-859.Anderson O. S., Sant K. E., Dolinoy D. C. Nutrition and epigenetics: an 2014interplay of dietary methyl donors, one-carbon metabolism and DNA methylation. J. Nutr. Biochem. 2012; 23: 853-859.Manikkam M., Tracey R., GuerreroBosagna C., Skinner M. K. Plastics derived endocrine disruptors (BPA, DEHP and DBP) induce epigenetic transgenerational inheritance of obesity, reproductive disease and sperm epimutations. PLoS One. 2013; 8(1), e55387, 10.1371/journal. pone.0055387Manikkam M., Tracey R., GuerreroBosagna C., Skinner M. K. Plastics derived endocrine disruptors (BPA, DEHP and DBP) induce epigenetic transgenerational inheritance of obesity, reproductive disease and sperm epimutations. PLoS One. 2013; 8(1), e55387, 10.1371/journal. pone.0055387Dosunmu R., Alashwal H., Zawia N. H. (2012). Genome-wide expression and methylation profiling in the aged rodent brain due to early-life Pb exposure and its relevance to aging. Mech. Ageing Dev. 2012; 133: 435-443.Dosunmu R., Alashwal H., Zawia N. H. (2012). Genome-wide expression and methylation profiling in the aged rodent brain due to early-life Pb exposure and its relevance to aging. Mech. Ageing Dev. 2012; 133: 435-443.Marco A., Kisliouk T., Tabachnik T., Meiri N., Weller A. Overweight and CpG methylation of the Pomc promoter in offspring of high-fat-diet-fed dams are not “reprogrammed” by regular chow diet in rats. FASEB J. 2014; 28: 4148-4157.Marco A., Kisliouk T., Tabachnik T., Meiri N., Weller A. Overweight and CpG methylation of the Pomc promoter in offspring of high-fat-diet-fed dams are not “reprogrammed” by regular chow diet in rats. FASEB J. 2014; 28: 4148-4157.Guerrero-Bosagna C., Covert T. R., Haque M. M., Settles M., et al. Epigenetic transgenerational inheritance of vinclozolin induced mouse adult onset disease and associated sperm epigenome biomarkers. Reprod. Toxicol. 2012; 34: 694-707.Guerrero-Bosagna C., Covert T. R., Haque M. M., Settles M., et al. Epigenetic transgenerational inheritance of vinclozolin induced mouse adult onset disease and associated sperm epigenome biomarkers. Reprod. Toxicol. 2012; 34: 694-707.Reichard J.F., Puga A. Effects of arsenic exposure on DNA methylation and epigenetic gene regulation. Epigenomics. 2010; 2: 87-104.Reichard J.F., Puga A. Effects of arsenic exposure on DNA methylation and epigenetic gene regulation. Epigenomics. 2010; 2: 87-104.Kim J. H., Sartor M. A., Rozek L. S., Faulk C., et al. Perinatal bisphenol A exposure promotes dose-dependent alterations of the mouse methylome. BMC Genomics. 2014; 15:Kim J. H., Sartor M. A., Rozek L. S., Faulk C., et al. Perinatal bisphenol A exposure promotes dose-dependent alterations of the mouse methylome. BMC Genomics. 2014; 15:Gilbert, K. M., Nelson, A. R., Cooney, C. A., Reisfeld, B., and Blossom, S. J. (2012). Epigenetic alterations may regulate temporary reversal of CD4(+) T cell activation caused by trichloroethylene exposure. Toxicol Sci 127(1), 169-78Gilbert, K. M., Nelson, A. R., Cooney, C. A., Reisfeld, B., and Blossom, S. J. (2012). Epigenetic alterations may regulate temporary reversal of CD4(+) T cell activation caused by trichloroethylene exposure. Toxicol Sci 127(1), 169-78Arita A., Shamy M. Y., Chervona Y., Clancy H. A., et al. The effect of exposure to carcinogenic metals on histone tail modifications and gene expression in human subjects. J. Trace. Elem. Med. Biol. 2012; 26: 174-178.Arita A., Shamy M. Y., Chervona Y., Clancy H. A., et al. The effect of exposure to carcinogenic metals on histone tail modifications and gene expression in human subjects. J. Trace. Elem. Med. Biol. 2012; 26: 174-178.Veazey K. J., Parnell S. E., Miranda R. C., Golding M. C. Dose-dependent alcoholinduced alterations in chromatin structure persist beyond the window of exposure and correlate with fetal alcohol syndrome birth defects. Epigenetics Chromatin. 2015; 8:Veazey K. J., Parnell S. E., Miranda R. C., Golding M. C. Dose-dependent alcoholinduced alterations in chromatin structure persist beyond the window of exposure and correlate with fetal alcohol syndrome birth defects. Epigenetics Chromatin. 2015; 8:Tammen S. A., Dolnikowski G. G., Ausman L. M., Liu Z., et al.).Aging and alcohol interact to alter hepatic DNA hydroxymethylation. Alcohol. Clin. Exp. Res. 2014; 38: 2178-2185.Tammen S. A., Dolnikowski G. G., Ausman L. M., Liu Z., et al.).Aging and alcohol interact to alter hepatic DNA hydroxymethylation. Alcohol. Clin. Exp. Res. 2014; 38: 2178-2185.Patkin E.L., Pavlinova L.I., Noniashvili E.M., Sasina L.K., Grudinina N.A., Kolmakov N.N., Suchkova I.O., Tranvan Truong, Sofronov G.A. Asymmetric DNA methylation between sister chromatids of metaphase chro mosomes in preimplantation mouse embryos and two cell lines upon Bisphenol A action. Reprod. Toxicol. 2017; Aug 24;74:1-doi: 6/j.reprotox.2017.08.017.Patkin E.L., Pavlinova L.I., Noniashvili E.M., Sasina L.K., Grudinina N.A., Kolmakov N.N., Suchkova I.O., Tranvan Truong, Sofronov G.A. Asymmetric DNA methylation between sister chromatids of metaphase chro mosomes in preimplantation mouse embryos and two cell lines upon Bisphenol A action. Reprod. Toxicol. 2017; Aug 24;74:1-doi: 6/j.reprotox.2017.08.017.Нониашвили Е. М., Грудинина Н.А., Кустова М.Е., Чан В.Ч., Сучкова И. О., Павлинова Л.И., Сасина Л. К., Дергачева Н.И., Софронов Г.А., Паткин Е. Л. Метилирование ДНК в раннем эмбриогенезе мышей под влиянием бисфенола А. Экологическая генетика. 2017; 15: 42–/ E.M.Noniashvili, N.A.Grudinina, M.E.Kustova, V.T. Tran, I.O.Suchkova, L.I.Pavlinova, L.K.Sasina, N.I.Dergacheva, G.A.Sofronov, E.L.Patkin.Нониашвили Е. М., Грудинина Н.А., Кустова М.Е., Чан В.Ч., Сучкова И. О., Павлинова Л.И., Сасина Л. К., Дергачева Н.И., Софронов Г.А., Паткин Е. Л. Метилирование ДНК в раннем эмбриогенезе мышей под влиянием бисфенола А. Экологическая генетика. 2017; 15: 42–/ E.M.Noniashvili, N.A.Grudinina, M.E.Kustova, V.T. Tran, I.O.Suchkova, L.I.Pavlinova, L.K.Sasina, N.I.Dergacheva, G.A.Sofronov, E.L.Patkin.DNA methylation in early mice embryogenesis under the influence of bisphenol A.DNA methylation in early mice embryogenesis under the influence of bisphenol A.Ecological genetics. 2017; 15:42-(in Russian).Ecological genetics. 2017; 15:42-(in Russian).Johnson C.H., Patterson A.D., Idle J.R., Gonzalez F.J..Xenobiotic Metabolomics: Major Impact on the Metabolome. Annu. Rev. Pharmacol. 2012; 52:37–56.Johnson C.H., Patterson A.D., Idle J.R., Gonzalez F.J..Xenobiotic Metabolomics: Major Impact on the Metabolome. Annu. Rev. Pharmacol. 2012; 52:37–56.Migicovsky Z., Kovalchuk I. Epigenetic memory in mammals. Front. Genet. 2011; 2:28.Migicovsky Z., Kovalchuk I. Epigenetic memory in mammals. Front. Genet. 2011; 2:28.Ho S.M., Johnson A., Tarapore P., Janakiram V., Zhang X., Leung Y.K. Environmental epigenetics and its implication on disease risk and health outcomes. ILAR J. 2012; 53:289–305.Ho S.M., Johnson A., Tarapore P., Janakiram V., Zhang X., Leung Y.K. Environmental epigenetics and its implication on disease risk and health outcomes. ILAR J. 2012; 53:289–305.Jimenez-Chillaron J.C., Nijland M.J., A Ascensao A.A., Vilma A Sardao V.A., et al. Back to the future: transgenerational transmission of xenobiotic-induced epigenetic remodeling. Epigenetics. 2015; 10: 259-2Jimenez-Chillaron J.C., Nijland M.J., A Ascensao A.A., Vilma A Sardao V.A., et al. Back to the future: transgenerational transmission of xenobiotic-induced epigenetic remodeling. Epigenetics. 2015; 10: 259-2Emma C. Bowers E.C., Shaun D. McCullough S.D. Linking the Epigenome with Exposure Effects and Susceptibility: The Epigenetic Seed and Soil Model. Toxicol. Sci. 2017; 155:302-3Emma C. Bowers E.C., Shaun D. McCullough S.D. Linking the Epigenome with Exposure Effects and Susceptibility: The Epigenetic Seed and Soil Model. Toxicol. Sci. 2017; 155:302-3Baylin S. B. DNA methylation and gene silencing in cancer. Nat. Clin. Pract. Oncol. 2005; 2: S4-SBaylin S. B. DNA methylation and gene silencing in cancer. Nat. Clin. Pract. Oncol. 2005; 2: S4-SSmith Z. D., Meissner A. DNA methylation: roles in mammalian development. Nat. Rev. Genet. 2013; 14: 204-220.Smith Z. D., Meissner A. DNA methylation: roles in mammalian development. Nat. Rev. Genet. 2013; 14: 204-220.Bollati V., Baccarelli A. Environmental epigenetics. Heredity. 2010; 105: 105- 112.Bollati V., Baccarelli A. Environmental epigenetics. Heredity. 2010; 105: 105- 112.Koturbash I., Beland F. A., Pogribny I. P. Role of epigenetic events in chemical carcinogenesis—a justification for incorporating epigenetic evaluations in cancer risk assessment. Toxicol. Mech. Method. 2011; 2: 289-297.Koturbash I., Beland F. A., Pogribny I. P. Role of epigenetic events in chemical carcinogenesis—a justification for incorporating epigenetic evaluations in cancer risk assessment. Toxicol. Mech. Method. 2011; 2: 289-297.Софронов Г.А., Чинь Куок Кхань, Кузнецов А.Н., Павлов Д.С., Румак В.С. Воздействие диоксинов на окружающую среду и здоровье человека. Вестник РАН. 2009; 79:124-1/ G.A.Sofronov, Chin Kuok Khan, Kuznetsov A.N., Pavlov D.S., Rumak V.S. The influence of dioxins on environment and human health. Vestnik RAN.2009; 79: 124-130 (in Russian).Софронов Г.А., Чинь Куок Кхань, Кузнецов А.Н., Павлов Д.С., Румак В.С. Воздействие диоксинов на окружающую среду и здоровье человека. Вестник РАН. 2009; 79:124-1/ G.A.Sofronov, Chin Kuok Khan, Kuznetsov A.N., Pavlov D.S., Rumak V.S. The influence of dioxins on environment and human health. Vestnik RAN.2009; 79: 124-130 (in Russian).Marczylo E.L., Miriam N., Jacobs M.N., Gant T.W. Environmentally induced epigenetic toxicity: potential public health concerns. Critical Reviews Toxicol. 2016; 46: 676–700.Marczylo E.L., Miriam N., Jacobs M.N., Gant T.W. Environmentally induced epigenetic toxicity: potential public health concerns. Critical Reviews Toxicol. 2016; 46: 676–700.Abdul Q.A., Yu B.P., Chung H.Y., Jung H.A., Choi J.S. Epigenetic modifications of gene expression by lifestyle and environment. Arch Pharm Res. 2017; Oct doi: 10.1007/s12272-017-0973-3.Abdul Q.A., Yu B.P., Chung H.Y., Jung H.A., Choi J.S. Epigenetic modifications of gene expression by lifestyle and environment. Arch Pharm Res. 2017; Oct doi: 10.1007/s12272-017-0973-3.Denham J. Exercise and epigenetic inheritance of disease risk. Acta Physiol. (Oxf). 2017; Mar doi: 10.1111/ apha.12881.Denham J. Exercise and epigenetic inheritance of disease risk. Acta Physiol. (Oxf). 2017; Mar doi: 10.1111/ apha.12881.

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