Environmental toxicants, incidence of degenerative diseases, and therapies from the epigenetic point of view (original) (raw)
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Effect of Environmental Chemical Exposures on Epigenetics of Diseases: A Systematic Review
Every year more than 13 million deaths worldwide are due to environmental pollutants, and approximately 24% of diseases are caused by environmental exposures that might be averted through preventive measures. Out of all these environmental chemicals, effects of air pollution is responsible for death of 3.3 million people prematurely worldwide-a figure that could double by 2050 if emissions continue to rise at the current rate. Increasing number of evidences has linked environmental pollutants with epigenetic variations, including changes in DNA methylation status, histone modifications and other factors like incorporation of miRNAs, nucleosome remodeling, etc. These entire mechanisms are likely to play important roles in disease aetiology, and their modifications, thus providing further understanding of disease aetiology, as well as biomarkers for these exposures to environmental chemicals and/or prediction of the risk for the disease. In this, we had tried to summarize the different epigenetic alterations related to environmental chemical exposures, and propose the probable mechanisms of action behind such epigenetic changes. We will also focus onopportunities, challenges and further directions for future epidemiology research in environmental epigenomics. Further studies are needed in this regard to solve methodological and practical challenges, including uncertainties about stability over time of epigenomic changes induced by the environment, tissue specificity of epigenetic alterations, validation of laboratory methods, and adaptation of bioinformatic and biostatistical methods to high-throughput epigenomics. Moreover, there are several reports of epigenetic modifications arising from environmental chemical exposures, but most have not been directly linked to disease endpoints.
Environmental Epigenetics: Crossroad between Public Health, Lifestyle, and Cancer Prevention
BioMed Research International, 2015
Epigenetics provides the key to transform the genetic information into phenotype and because of its reversibility it is considered an ideal target for therapeutic interventions. This paper reviews the basic mechanisms of epigenetic control: DNA methylation, histone modifications, chromatin remodeling, and ncRNA expression and their role in disease development. We describe also the influence of the environment, lifestyle, nutritional habits, and the psychological influence on epigenetic marks and how these factors are related to cancer and other diseases development. Finally we discuss the potential use of natural epigenetic modifiers in the chemoprevention of cancer to link together public health, environment, and lifestyle.
Environmentally induced epigenetic toxicity: potential public health concerns
Critical Reviews in Toxicology
Throughout our lives, epigenetic processes shape our development and enable us to adapt to a constantly changing environment. Identifying and understanding environmentally induced epigenetic change(s) that may lead to adverse outcomes is vital for protecting public health. This review, therefore, examines the present understanding of epigenetic mechanisms involved in the mammalian life cycle, evaluates the current evidence for environmentally induced epigenetic toxicity in human cohorts and rodent models and highlights the research considerations and implications of this emerging knowledge for public health and regulatory toxicology. Many hundreds of studies have investigated such toxicity, yet relatively few have demonstrated a mechanistic association among specific environmental exposures, epigenetic changes and adverse health outcomes in human epidemiological cohorts and/or rodent models. While this small body of evidence is largely composed of exploratory in vivo high-dose range studies, it does set a precedent for the existence of environmentally induced epigenetic toxicity. Consequently, there is worldwide recognition of this phenomenon, and discussion on how to both guide further scientific research towards a greater mechanistic understanding of environmentally induced epigenetic toxicity in humans, and translate relevant research outcomes into appropriate regulatory policies for effective public health protection.
Here it is shown that investigation of DNA methylation using pyrosequencing is an alternative for in vitro and in vivo toxicological testing of epigenetic effects induced by chemicals and drugs. An in vitro evaluation of global and CpG site specific DNA methylation upon treatment of cells with chemicals/drugs is shown. Bisulfite genomic sequencing of methylation controls showed high methylation of LINE1 in methylation positive control and low methylation in the negative controls. The CpG sites within the LINE1 element are methylated at different levels. In vitro cell cultures show a methylation level ranging from 56% to 49%. Cultures of drug resistant tumor cells show significant hypomethylation as compared with the originating nonresistant tumor cells. The in vitro testing of epigenetically active chemicals (5-methyl-2'-deoxycytidine and trichostatin A) revealed a significant change of LINE1 methylation status upon treatment, while specific CpG sites were more prone to demethylation than others (focal methylation). In conclusion, DNA methylation using pyrosequencing might be used not only for testing epigenetic toxins/drugs but also in risk assessment of drugs, food, and environmental relevant pollutants.
Recent advances in understanding/assessing toxicity to the epigenome
F1000Research, 2017
The ability of non-genotoxic agents to induce cancer has been documented and clearly requires a reassessment of testing for environmental and human safety. Drug safety testing has historically relied on test batteries designed to detect DNA damage leading to mutation and cancer. The standard genetic toxicology testing battery has been a reliable tool set to identify small molecules/chemicals as hazards that could lead to genetic changes in organisms and induction of cancer. While pharmaceutical companies and regulatory agencies have extensively used the standard battery, it is not suitable for compounds that may induce epigenetic changes. Additionally, many pharmaceutical companies have changed their product portfolios to include peptides and/or other biological molecules, which are not expected to be genotoxic in their own right. If we are to best use our growing knowledge regarding chemicals and biomolecules that induce heritable changes via epigenetic mechanisms, then we must ask...
The Role of Environmental Exposures and the Epigenome in Health and Disease
Environmental and Molecular Mutagenesis
The genetic material of every organism exists within the context of regulatory networks that govern gene expression, collectively called the epigenome. Epigenetics has taken center stage in the study of diseases such as cancer and diabetes, but its integration into the field of environmental health is still emerging. As the Environmental Mutagenesis and Genomics Society (EMGS) celebrates its 50th Anniversary this year, we have come together to review and summarize the seminal advances in the field of environmental epigenomics. Specifically, we focus on the role epigenetics may play in multigenerational and transgenerational transmission of environmentally induced health effects. We also summarize state of the art techniques for evaluating the epigenome, environmental epigenetic analysis, and the emerging field of epigenome editing. Finally, we evaluate transposon epigenetics as they relate to environmental exposures and explore the role of noncoding RNA as biomarkers of environmental exposures. Although the field has advanced over the past several decades, including being recognized by EMGS with its own Special Interest Group, recently renamed Epigenomics, we are excited about the opportunities for environmental epigenetic science in the next 50 years.
Cancer Susceptibility: Epigenetic Manifestation of Environmental Exposures
The Cancer Journal, 2007
Cancer is a disease that results from both genetic and epigenetic changes. Discordant phenotypes and varying incidences of complex diseases such as cancer in monozygotic twins as well as genetically identical laboratory animals have long been attributed to differences in environmental exposures. Accumulating evidence indicates, however, that disparities in gene expression resulting from variable modifications in DNA methylation and chromatin structure in response to the environment also play a role in differential susceptibility to disease. Despite a growing consensus on the importance of epigenetics in the etiology of chronic human diseases, the genes most prone to epigenetic dysregulation are incompletely defined. Moreover, neither the environmental agents most strongly affecting the epigenome nor the critical windows of vulnerability to environmentally induced epigenetic alterations are adequately characterized. These major deficits in knowledge markedly impair our ability to understand fully the etiology of cancer and the importance of the epigenome in diagnosing and preventing this devastating disease.
Mechanisms of Epigenetic Toxicity in the Pathogenesis of Cancer for "Precision Medicine
Journal of Cancer Treatment and Diagnosis
While the concept of "precision medicine" is not new, sophisticated technologies have led to a view that the data generated will provide individuals, physicians and public policy-makers with the information required to predict, intervene and protect against many diseases. However, without understanding of the underlying molecular mechanisms, such as the mutagenicity, cytotoxicity or epigenetic alterations, induced by agents to which a human has been exposed, and with pathogenic events, such as birth defects, cardiovascular disease, cancer, immune responses, and reproductive or neurological diseases, there will be no "precision". The aim of this "Commentary" is that, while mutations and cell death contribute to human diseases, including cancers, the toxicity of chemicals is primarily due to epigenetic effects on human organspecific adult stem cells. From the perspective of biological evolution, the transition from single-to multi-cellular organisms, along with the generation of new genes and cellular processes, led to the evolution of Homo sapiens and "cultural evolution". This transition has created a "collision" of the slow biological evolution of genes that are important for survival in various environments, with extremely fast cultural evolution. This has occurred when cultural evolution has provided new means of migration for both people and foods, as well as new methods of agriculture and food production/distribution/ processing. The population explosion, ecological alterations, global climate changes, and worldwide economic disparities all have a bearing on how the increases in median life span and the incidence of chronic metabolic diseases are managed in the face of globally limited healthcare resources.
Epigenetics mechanisms and degenerative diseases
Open Journal of Genetics, 2012
Epigenetic regulations are heritable changes in gene expression that occur in the absence of alterations in DNA sequences. Various epigenetic mechanisms include histone modifications and DNA methylations. In this review, we examine methods to study DNA methylations and their contribution to degenerative diseases by mediating the complex gene-by-environment interactions. Such epigenetic modifications despite being heritable and stably maintained are also potentially reversible and there is scope for the development of epigenetic therapies for this disease.
The Dynamic Epigenome and its Implications in Toxicology
Toxicological Sciences, 2007
The epigenome serves as an interface between the dynamic environment and the inherited static genome. The epigenome is comprised of chromatin and a covalent modification of DNA by methylation. The epigenome is sculpted during development to shape the diversity of gene expression programs in the different cell types of the organism by a highly organized process. Epigenetic aberrations have similar consequences to genetic polymorphisms resulting in variations in gene function. Recent data suggest that the epigenome is dynamic and is therefore responsive to environmental signals not only during the critical periods in development but also later in life as well. It is postulated here that not only chemicals but also exposure to social behavior, such as maternal care, could affect the epigenome. It is proposed that exposures to different environmental agents could lead to interindividual phenotypic diversity as well as differential susceptibility to disease and behavioral pathologies. Interindividual differences in the epigenetic state could also affect susceptibility to xenobiotics. Although our current understanding of how epigenetic mechanisms impact on the toxic action of xenobiotics is very limited, it is anticipated that in the future, epigenetics will be incorporated in the assessment of the safety of chemicals.