Advisor: Bryant C. Nelson
Keywords: Cytotoxicity; Engineered Nanomaterials; Free Radicals; Gas Chromatography/Tandem Mass Spectrometry; Genotoxicity, Liquid Chromatography/Tandem Mass Spectrometry; Metabolites; Metabolomics; Oxidative Stress;
We are interested in developing and applying mass spectrometry-based metabolomics to the study of nanomaterial-induced toxicity and DNA damage in Caenorhabditis elegans (C. elegans). C. elegans represents an ideal in vivo system for these types of investigations due to its strong genetic similarity to humans and to 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 over time. The genetic composition of a C. elegans strain is a constant and it is also possible to precisely control the environmental growing conditions of the worm. Thus, following exposure to redox-active nanoparticles, it is probable that the molecular profiles of the worm metabolites in specific biological pathways can be quantitatively correlated to the accumulation of oxidatively induced DNA modifications (DNA lesions). The correlation between the profiles of the metabolites/metabolic intermediates and the DNA lesions can assist in defining the toxicity repertoire of engineered nanomaterials. To this end, research is on-going in the design and development of advanced mass spectrometry platforms for quantitatively interrogating changes in the levels of targeted energy metabolites that are intimately involved in nucleotide synthesis, glycolysis and citric acid cycle metabolism. Our laboratory utilizes state-of-the-art tandem mass spectrometry instrumentation, with both liquid and gas chromatographic interfaces, for metabolomic profiling. The goal of this new research area is to develop comprehensive strategies and advanced measurement applications for understanding the interaction of engineered nanomaterials with discrete intra-cellular molecules and how those nanomaterial-molecule interactions mediate in vivo toxicity.
Bryant C. Nelson, Ph.D. NanoGenotoxicology Project Leader, National Institute of Standards and Technology (NIST), Biochemical Science Division, 301-975-2517 (office). http://www.nist.gov/mml/biochemical/dna/bryant-nelson.cfm