Chemicals can alter epigenetic marks, and same epigenetic alterations can be found in patients with the disease of concern or in diseased tissues
2009 Study Abstract
PURPOSE OF REVIEW
Epigenetics investigates heritable changes in gene expression occurring without changes in DNA sequence. Several epigenetic mechanisms, including DNA methylation, histone modifications, and microRNA expression, can change genome function under exogenous influence. Here, we review current evidence indicating that epigenetic alterations mediate toxicity from environmental chemicals.
RECENT FINDINGS
In-vitro, animal, and human investigations have identified several classes of environmental chemicals that modify epigenetic marks, including metals (cadmium, arsenic, nickel, chromium, and methylmercury), peroxisome proliferators (trichloroethylene, dichloroacetic acid, and TCA), air pollutants (particulate matter, black carbon, and benzene), and endocrine-disrupting/reproductive toxicants (diethylstilbestrol, bisphenol A, persistent organic pollutants, and dioxin). Most studies conducted so far have been centered on DNA methylation, whereas only a few investigations have studied environmental chemicals in relation to histone modifications and microRNA.
SUMMARY
For several exposures, it has been proved that chemicals can alter epigenetic marks, and that the same or similar epigenetic alterations can be found in patients with the disease of concern or in diseased tissues. Future prospective investigations are needed to determine whether exposed individuals develop epigenetic alterations over time and, in turn, which such alterations increase the risk of disease. Also, further research is needed to determine whether environmental epigenetic changes are transmitted transgenerationally.
Diethylstilbestrol
DES is a developmental stage-specific non-genotoxic carcinogen that was used in the past to prevent miscarriages in pregnant women. In mice models, pre- and neonatal DES exposure causes a wide range of gene expression changes. Exogenous estrogen treatment results in persistent expression of certain genes, including lactoferrin, epidermal growth factor, and protooncogenes such as c-fos, c-jun and c-myc. Research has provided data supporting an indirect relationship between exogenous estrogen and methylation changes, showing that estrogen inhibited catechol-O-methyltransferase (COMT) gene transcription. COMT is an ubiquitous enzyme catalyzing the transfer of the methyl groups from SAM to one of the hydroxyl groups of catechols in presence of Mg2+. Inhibition of this enzyme results in inhibition of the methylation process.
Conclusions
In the last few years, several investigations have examined the relation between exposure to environmental chemicals and epigenetics, and identified several toxicants that modify epigenetic marks. Most of the studies conducted so far have been centered on DNA methylation, whereas only a few recent investigations have studied the effects of environmental chemicals on histone modications and miRNA. Epigenetics holds substantial potential for developing biological markers to predict which exposures would put exposed subjects at risk and which individuals will be more susceptible to develop disease. In human studies, this will require the use of laboratory methods with enhanced precision and sensitivity, so that epigenetic changes can be detected as early as possible and well ahead of disease diagnosis. It is worth noting that several human studies have investigated the effects of environmental exposures on tissues, such as blood, that are easy to obtain, but that, as effects of environmental chemicals may be tissue or even cell specific, do not necessarily represent epigenetic patterns in the target tissues. For several exposures, however, it has been proved that chemicals can alter epigenetic marks and that the same or similar epigenetic alterations can be found in patients with the disease of concern or in diseased tissues. At the current stage, the missing link is to determine whether environmentally-induced epigenetic alterations are part of the causative pathways that leads to the disease development. Future prospective investigations are needed to determine whether exposed subjects develop epigenetic alterations over time and, in turn, whether such alterations increase the risk of disease.
Sources and more information
- Full study (free access) Epigenetics and environmental chemicals, Current Opinion Pediatrics, NCBI PubMed PMC3035853, 2009 Apr.
- Potential mechanisms linking environmental exposures to epigenetic effects featured image credit PMC2855843/figure/F1.
DES DIETHYLSTILBESTROL RESOURCES
- Source DES and epigenetics studies.
- Diethylstilbestrol DES studies by topics.