Environmentally induced epigenetic toxicity: potential public health concerns

Abstract

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.

International regulatory needs for development ofan IATA for non-genotoxic carcinogenic chemical substances

“…However, the induction of oxidative stress may also regulate gene expression either directly through activation of gene transcriptional pathways or indirectly through hypomethylation (Nishida and Kudo, 2013;Casey et al, 2015;Vaccari et al, 2015;Wu and Ni, 2015). Epigenetic mechanisms in relation to regulatory needs are reviewed by Greally and Jacobs (2013) and Marczylo et al (2016), and International Agency for Research on Cancer (IARC) cancer classification by Herceg et al (2013). Taken together, these reviews demonstrate the major roles that such epigenetic mechanisms can play in tumor formation, often in combination with other mechanisms, and how this understanding can start to be applied for OECD and IARC purposes.…”

Immunotoxicity, genotoxicity and epigenetic toxicity of nanomaterials: New strategies for toxicity testing?

“…The epigenetic alterations driven by NMs, especially soft particles, have rarely been studied. A growing body of evidence indicates that environmentally-induced epigenetic alterations play a role in the onset of several human diseases, including cancer, mental disorders, obesity, and other severe conditions (reviewed in (Marczylo et al, 2016). At this point, a wellstandardized animal-free approach to study epimutagens is not yet available.…”

Editorial overview of the special issue on genomic toxicology epigenetics

“…In the mammalian genome, negatively charged linear DNA is compacted into chromatin, which is dynamic and subject to epigenetic modifications that include cytosine DNA methylation, posttranslational modifications of histone proteins, and nucleosome positioning along DNA. It is well established that environmental, occupational, or lifestyle exposures may affect both the genome, through DNA damage and mutations, and the epigenome [1,2]. Despite the growing body of evidence that the epigenome is a target for toxicants, there is still lack of clarify on what role, if any, these toxicant-induced epigenetic alterations may play with respect to causality of the associated adverse health outcomes.…”