Changes in DNA Methylation Induced by Dioxins and Dioxin-Like Compounds as Potential Predictor of Disease Risk
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EWS AND THEORETICAL ARTICLES
Changes in DNA Methylation Induced by Dioxins and Dioxin-Like Compounds as Potential Predictor of Disease Risk N. S. Kuzminaa, *, T. M. Luongb, and A. V. Rubanovicha aVavilov
bJoint
Institute of General Genetics, Russian Academy of Sciences, Moscow, 119991 Russia Russian-Vietnamese Tropical Research and Technological Center, South Branch, 3, Ho Chi Minh City, Vietnam *e-mail: [email protected] Received December 10, 2019; revised January 15, 2020; accepted January 20, 2020
Abstract—Dioxins and dioxin-like compounds are persistent organic pollutants (POPs) and technogenic ecotoxicants, the most dangerous of which is 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). A peculiar feature of the considered genotoxicants that distinguishes them from other POPs is hormone-like activity, which is realized through binding to a special cellular protein, the Aryl hydrocarbon Receptor (AhR). In the present study, the phenomenological aspects of DNA methylation changes induced by dioxins and dioxin-like compounds and revealed in the studies in vitro and in vivo are considered. In animal models, multigenerational and transgenerational effects of dioxin-induced locus-specific DNA methylation changes and their association with reproductive dysfunctions and congenital malformations were firmly established. The importance of investigations of the long-term epigenetic consequences of human exposure to dioxins and the potential value of such studies for preventive diagnostics of somatic and reproductive pathologies are discussed. Keywords: dioxins, DNA methylation, transgenerational effects, aging-associated and reproductive pathologies DOI: 10.1134/S1022795420100063
INTRODUCTION Environmental safety issues are closely associated with the environmental ubiquity of persistent organic pollutants (POPs), which include organochlorine pesticides (DDT, aldrin, chlordane, hexachlorobenzene, mirex, etc.), polychlorinated biphenyls (PCBs), polychlorodibenzodioxins (PCDD), and polychlorodibenzofurans (PCDF). These compounds are characterized by very high toxicity, resistance to the destructive action of different factors, pronounced persistence, excessive accumulation and bioaccumulation, metabolic activation, and migration to new territories from the primary source of pollution [1–3]. Although the production and use of a number of POPs listed in the Stockholm Convention (organochlorine pesticides) were banned, there are still a number of more toxic dioxins (PCDDs) and dioxin-like compounds (PCBs and PCDFs), which are by-products of various industrial processes (production of herbicides and pesticides, oil refining, electrical engineering, pulp and paper industry, chemical industry, waste incinerators, etc.). Therefore, persons employed in these industries, as well as residents of the territories adjacent to large enterprises, represent the risk groups for the development of pathologies induced by the considerated genotoxicants.
Dioxins is a common name for a large group of heterocyclic polychlorinated compounds, in
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