Our laboratory is developing and applying mass spectrometry-based metabolomics to the
study of nanomaterial-induced toxicity and DNA damage in the Caenorhabditis elegans
(C. elegans) nematode. C. elegans represents an ideal in vivo system for these types of
investigations due to its strong genetic homology with humans (60 to 80% homologous),
its short life-span (2 to 3 weeks) and its sensitivity to oxidative stress inducing agents.
Recent investigations have shown that certain types of engineered nanomaterials, e.g.,
silver nanoparticles, can induce oxidative stress in cultured cells purportedly due to an
increase in the levels of reactive oxygen species (ROS) and/or to a decrease in the levels
or activities of antioxidants. ROS, in the form of free radicals, can perturb the levels of
endogenous cellular metabolites and metabolic intermediates in a defined manner over
time. Nevertheless, the genetic composition of a particular C. elegans strain will remain
constant and it is also possible to precisely control the environmental growing conditions
of the worm. Thus, following exposure to redox-active nanoparticles, the molecular
profiles of worm metabolites involved in central metabolism can be quantitatively
correlated to the accumulation of oxidatively induced DNA modifications (mutagenic and
cytotoxic DNA lesions). The correlation among the profiles of the metabolites/metabolic
intermediates and the DNA lesion levels can potentially assist in characterizing and
defining the toxicity repertoire of engineered nanomaterials in selected classes. To this
end, our laboratory is designing, developing and applying advanced mass spectrometry
platforms for quantitatively interrogating changes in the levels of central metabolism
intermediates that are intimately involved in nucleotide synthesis, glycolysis and citric
acid cycle metabolism. We utilize state-of-the-art tandem mass spectrometry
instrumentation, with both liquid and gas chromatographic interfaces, for metabolomic
profiling. The goals of this emerging research area are (1) to develop comprehensive
strategies and advanced measurement tools/applications for understanding the interaction
of nanomaterials with discrete intra-cellular molecules (2) to define and describe in
quantitative terms how these nanomaterial-molecule interactions mediate in vivo toxicity
and genomic DNA damage.
For information regarding NRC postdoctoral positions in this area, please contact:
Dr. Bryant C. Nelson
NIST
Material Measurement Laboratory
Gaithersburg, Maryland
301-975-2517
bryant.nelson@nist.gov