Project title: Differential Susceptibility to Quantum Dot Induced Lung Inflammation: A System Genetics Approach
Completed in: 2012 | Faculty advisor: Terrance J. Kavanagh
Quantum dots (QDs) are nanoparticles typically composed of a CdSe core, a ZnS shell, and an assortment of polymer coatings specific to their application. Unique fluorescent properties of QDs make them useful in biomedical imaging. However, due to their small size and heavy metal composition, there is concern over the possible toxicity of QDs. We have examined 8 genetically inbred parental mouse strains from the Collaborative Cross (CC) for their differential susceptibility to QD-induced lung inflammation using % neutrophils and total protein in bronchoalveolar lavage fluid (BALF) as inflammation biomarkers. Oropharyngeal aspiration was used to deliver a 6 f Cd equivalents/kg BW dose of QDs into the lungs of the different strains of mice. Flow cytometry and the Bradford Assay were used to measure the % neutrophils and total protein in BALF, respectively. In an attempt to explore whether mechanisms that are currently thought to mediate QD toxicity seem to be playing a role in these mice, Cd and total GSH levels were measured in lung tissue using ICP-MS, and derivatization with naphthalene-2,3-dicarboxaldehyde (NDA) with fluorescence detection, respectively. Significant variation was observed in biomarkers of QD induced inflammation, due to both QD treatment and genetic differences among mouse strains. In our exploration of Cd and GSH, an interaction was observed between GSH and the % neutrophils in BALF. Inverse correlations were seen between mean GSH levels and % neutrophils in BALF in all treatment groups we also observed that Cd levels positively correlated with the % of neutrophils in BALF, and that GSH and Cd are inversely correlated, possibly indicating that QDs are releasing Cd, depleting GSH and resulting in oxidative stress. Future studies using recombinant inbred Diversity Outcross strains created from the Collaborative Cross will be used to map potential quantitative trait loci (QTLs) associated with QD-induced lung inflammation and oxidative stress. Analysis of such QTLs could lead to insights regarding the molecular mechanisms responsible for QD toxicity and ultimately provide guidance to manufacturers on how to produce safer QDs.