Abstract
The diagnosis and treatment of diseases caused by the exposure of human epigenome to environmental pollutants are hampered by epigenomic plasticity, instability and nonlinear cumulative effects of existing transcriptional regulatory pathways. DNA methylation, histone acetylation and histone methylation are the best studied epigenetic modifications. There are simple methods for assessing genome-wide DNA methylation; however, it is essential to study the epigenetic landscape in detail in order to uncover the mechanisms underlying pollutant-associated effects on the organism. This prompts researchers to employ whole-genome sequencing and analyze vast arrays of sequencing data that can be compiled into extensive databases of human and animal epigenomes. Drugs developed to counter epigenetic disorders neutralize their symptoms and either affect epigenetic modifications across the entire genome or regulate the activity of enzymes that play a critical role in such disorders. Promise is held by targeted genome editing methods supported by modern technologies that are undergoing preclinical trials. This review discusses the potential of modern science in the diagnosis and treatment of diseases caused by environmental pollutants.
Highlights
It is reported that exposure to dioxin derivatives leads to the hypermethylation of CpG islands located in the imprinting control region of the murine Igf2 gene, whereas differential histone retention sites located upstream of the adjacent noncoding regions of the H19 gene are hypomethylated in comparison with the control group [29]
Bisphenol A directly interacts with S-adenosyl-methionine and at the same time modulates miRNA-29 expression via estrogen receptors [37]. This results in the decreased expression of DNA methyltransferases and the elevated expression of histone methyltransferase EZH2 implicated in repressive histone modification [38]
Organisms are exposed to a medley of pollutants, which produce an unpredictable interplay of effects, complicating the analysis of real populations vs. model objects. This problem can be solved by using data on the epigenetic modifications that are caused by known pollutants and produce known effects [39]
Summary
MODERN METHODS FOR ANALYSIS OF CHANGES TO EPIGENETIC LANDSCAPE CAUSED BY EXPOSURE TO ENVIRONMENTAL POLLUTANTS. The organs and systems that have direct contact with the pollutant sustain the most damage. Blood cells are affected as the main transport system of the body. The liver and kidneys can be damaged because of their leading role in the metabolism and excretion of toxic substances from the body. Systemic effects of pollutants on the human body include irritation; disrupted mucociliary clearance, which results in the increased permeability of the bronchial epithelium to allergens and infection and promotes the risk of asthma; neurogenic inflammation; lipid peroxidation activation and depression of the ROS metabolism system; hyperactivity of neutrophil elastase, which causes lung tissue damage; increased production of inflammatory mediators, like metabolites of arachidonic acid, cytokines and adhesion molecules
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