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the common baker's yeast, Saccharomyces cerevisiae, has about 600 metabo-
lites, the major ones having molecular weight below 300 g/mol (reviewed in
Oldiges et al. 2007). It has been projected that plants have more than 200,000
primary and secondary metabolites (Mungur et al. 2005).
Although far less mature than transcriptomics and proteomics, me-
tabolomics offers great promise for the development of early biomarkers of dis-
ease (Hollywood et al. 2006) and other uses of relevance to EPA. Because me-
tabolomics in many ways is the final integration of genomics, transcriptomics,
and proteomics, it is likely that future developments in this area will become
essential for understanding the functions of the genomes of organisms of interest
to EPA, ranging from pathogenic bacteria in drinking water to humans. Indeed,
EPA scientists are applying metabolomics approaches to aquatic toxicology
(Ekman et al. 2011), in vitro assessments for developmental toxicology (Klein-
streuer et al. 2011), and carcinogenic risk assessment (Wilson et al. 2012 in
press), to name a few.
EPIGENETICS
As noted by Rothstein et al. (2009), “epigenetics is one of the most scien-
tifically important, and legally and ethically significant, cutting-edge subjects of
scientific discovery.” Epigenetic changes are the chemical alterations or chemi-
cal modifications of DNA that do not involve changes in the nucleotide se-
quence in the DNA. Those alterations play a critical role in how and when a
particular gene is expressed. It is clear that environmental factors, including diet,
can influence how epigenetic regulation of gene expression occurs. It is espe-
cially important during periods of cell and tissue growth, such as embryonic and
fetal development. Epigenetic changes can be triggered by environmental fac-
tors. For example, exposure to metals, persistent organic pollutants, and some
endocrine disruptors modulate epigenetic markers in mammalian cells and in
other environmentally relevant species and have the potential to cause disease
(Vandegehuchte and Janssen 2011; Guerrero-Bosagna and Skinner 2012). Some
studies have demonstrated that epigenetic changes can sometimes be transferred
to later generations, even in the absence of the external factors that induced the
epigenetic changes (Skinner 2011).
EPA scientists in the National Health and Environmental Effects Research
Laboratory (NHEERL) are aware of the growing importance of epigenetics in
environmental health assessment. A seminal review of the application of epige-
netic mechanisms to carcinogenic risk assessment was published by NHEERL's
scientist Julian Preston (2007). Since then, relatively few publications from
NHEERL or other EPA laboratories have addressed epigenetics. A PubMed
search identified five publications by EPA scientists in the last 5 years. A recent
review by Jardim (2011) discussed the implications of microRNAs (a form of
epigenetic regulation of gene expression) for air-pollution research, and Lau et
al. (2011) reviewed fetal programming of adult disease (also thought to be an
epigenetic phenomenon) and its implications for prenatal care. Hsu et al. (2007)
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