title: Copper Oxide Nanoparticles Impact Several Toxicological Endpoints and Cause Neurodegeneration in Caenorhabditis elegans.
abstract: Engineered nanoparticles are becoming increasingly incorporated into technology and consumer products. In 2014, over 300 tons of copper oxide nanoparticles were manufactured in the United States. The increased production of nanoparticles raises concerns regarding the potential introduction into the environment or human exposure. Copper oxide nanoparticles commonly release copper ions into solutions, which contribute to their toxicity. We quantified the inhibitory effects of both copper oxide nanoparticles and copper sulfate on C. elegans toxicological endpoints to elucidate their biological effects. Several toxicological endpoints were analyzed in C. elegans, including nematode reproduction, feeding behavior, and average body length. We examined three wild C. elegans isolates together with the Bristol N2 laboratory strain to explore the influence of different genotypic backgrounds on the physiological response to copper challenge. All strains exhibited greater sensitivity to copper oxide nanoparticles compared to copper sulfate, as indicated by reduction of average body length and feeding behavior. Reproduction was significantly reduced only at the highest copper dose, though still more pronounced with copper oxide nanoparticles compared to copper sulfate treatment. Furthermore, we investigated the effects of copper oxide nanoparticles and copper sulfate on neurons, cells with known vulnerability to heavy metal toxicity. Degeneration of dopaminergic neurons was observed in up to 10% of the population after copper oxide nanoparticle exposure. Additionally, mutants in the divalent-metal transporters, smf-1 or smf-2, showed increased tolerance to copper exposure, implicating both transporters in copper-induced neurodegeneration. These results highlight the complex nature of CuO nanoparticle toxicity, in which a nanoparticle-specific effect was observed in some traits (average body length, feeding behavior) and a copper ion specific effect was observed for other traits (neurodegeneration, response to stress).
authors.affiliation: Department of Biological Sciences, Marquette University, Milwaukee, Wisconsin, United States of America.
authors.forename: Michael J
authors.identifier: http://orcid.org/0000-0003-0141-9770
authors.initials: MJ
authors.lastname: Mashock
authors.affiliation: Department of Biological Sciences, Marquette University, Milwaukee, Wisconsin, United States of America.
authors.forename: Tyler
authors.initials: T
authors.lastname: Zanon
authors.affiliation: Department of Biological Sciences, Marquette University, Milwaukee, Wisconsin, United States of America.
authors.forename: Anthony D
authors.initials: AD
authors.lastname: Kappell
authors.affiliation: Department of Biological Sciences, Marquette University, Milwaukee, Wisconsin, United States of America.
authors.forename: Lisa N
authors.initials: LN
authors.lastname: Petrella
authors.affiliation: Department of Molecular Biosciences, Northwestern University, Evanston, Illinois, United States of America.
authors.forename: Erik C
authors.initials: EC
authors.lastname: Andersen
authors.affiliation: Department of Biological Sciences, Marquette University, Milwaukee, Wisconsin, United States of America.
authors.forename: Krassimira R
authors.initials: KR
authors.lastname: Hristova
mesh_terms: D000818:Animals; D049628:Body Size / Q000187:drug effects / Q000235:genetics; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism; D027682:Cation Transport Proteins / Q000235:genetics / Q000378:metabolism; D003300:Copper / Q000633:toxicity*; D059290:Dopaminergic Neurons / Q000378:metabolism*; D005247:Feeding Behavior / Q000187:drug effects; D006801:Humans; D009154:Mutation; D053758:Nanoparticles / Q000633:toxicity*; D019636:Neurodegenerative Diseases / Q000139:chemically induced* / Q000235:genetics / Q000378:metabolism*
chemical_list: D029742:Caenorhabditis elegans Proteins; D027682:Cation Transport Proteins; C548880:smf-1 protein, C elegans; C548881:smf-2 protein, C elegans; D003300:Copper; C030973:cupric oxide