title: Susceptibility to quantum dot induced lung inflammation differs widely among the Collaborative Cross founder mouse strains.
abstract: Quantum dots (QDs) are engineered semiconductor nanoparticles with unique physicochemical properties that make them potentially useful in clinical, research and industrial settings. However, a growing body of evidence indicates that like other engineered nanomaterials, QDs have the potential to be respiratory hazards, especially in the context of the manufacture of QDs and products containing them, as well as exposures to consumers using these products. The overall goal of this study was to investigate the role of mouse strain in determining susceptibility to QD-induced pulmonary inflammation and toxicity. Male mice from 8 genetically diverse inbred strains (the Collaborative Cross founder strains) were exposed to CdSe-ZnS core-shell QDs stabilized with an amphiphilic polymer. QD treatment resulted in significant increases in the percentage of neutrophils and levels of cytokines present in bronchoalveolar lavage fluid (BALF) obtained from NOD/ShiLtJ and NZO/HlLtJ mice relative to their saline (Sal) treated controls. Cadmium measurements in lung tissue indicated strain-dependent differences in disposition of QDs in the lung. Total glutathione levels in lung tissue were significantly correlated with percent neutrophils in BALF as well as with lung tissue Cd levels. Our findings indicate that QD-induced acute lung inflammation is mouse strain dependent, that it is heritable, and that the choice of mouse strain is an important consideration in planning QD toxicity studies. These data also suggest that formal genetic analyses using additional strains or recombinant inbred strains from these mice could be useful for discovering potential QD-induced inflammation susceptibility loci.
authors.affiliation: Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA 98195, USA.
authors.forename: David K
authors.initials: DK
authors.lastname: Scoville
authors.affiliation: Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA 98195, USA.
authors.forename: Collin C
authors.initials: CC
authors.lastname: White
authors.affiliation: Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA 98195, USA.
authors.forename: Dianne
authors.initials: D
authors.lastname: Botta
authors.affiliation: Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA 98195, USA.
authors.forename: Lisa A
authors.initials: LA
authors.lastname: McConnachie
authors.affiliation: Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA 98195, USA.
authors.forename: Megan E
authors.initials: ME
authors.lastname: Zadworny
authors.affiliation: Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA 98195, USA.
authors.forename: Stefanie C
authors.initials: SC
authors.lastname: Schmuck
authors.affiliation: Department of Bioengineering, University of Washington, Seattle, WA 98195, USA.
authors.forename: Xiaoge
authors.initials: X
authors.lastname: Hu
authors.affiliation: Department of Bioengineering, University of Washington, Seattle, WA 98195, USA.
authors.forename: Xiaohu
authors.initials: X
authors.lastname: Gao
authors.affiliation: Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA 98195, USA.
authors.forename: Jianbo
authors.initials: J
authors.lastname: Yu
authors.affiliation: Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA 98195, USA.
authors.forename: Russell L
authors.initials: RL
authors.lastname: Dills
authors.affiliation: Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA 98195, USA; Department of Biostatistics, University of Washington, Seattle, WA 98195, USA.
authors.forename: Lianne
authors.initials: L
authors.lastname: Sheppard
authors.affiliation: Department of Comparative Medicine, University of Washington, Seattle, WA 98195, USA; Department of Pathology, University of Washington, Seattle, WA 98195, USA.
authors.forename: Martha A
authors.initials: MA
authors.lastname: Delaney
authors.affiliation: Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA 98195, USA.
authors.forename: William C
authors.initials: WC
authors.lastname: Griffith
authors.affiliation: Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA 98195, USA.
authors.forename: Richard P
authors.initials: RP
authors.lastname: Beyer
authors.affiliation: Systems Toxicology Group - Division of Biological Sciences, Pacific Northwest National Laboratory, Richland, WA 99352, USA.
authors.forename: Richard C
authors.initials: RC
authors.lastname: Zangar
authors.affiliation: Systems Toxicology Group - Division of Biological Sciences, Pacific Northwest National Laboratory, Richland, WA 99352, USA.
authors.forename: Joel G
authors.initials: JG
authors.lastname: Pounds
authors.affiliation: Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA 98195, USA.
authors.forename: Elaine M
authors.initials: EM
authors.lastname: Faustman
authors.affiliation: Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA 98195, USA. Electronic address: tjkav@uw.edu.
authors.forename: Terrance J
authors.initials: TJ
authors.lastname: Kavanagh
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D019187:Cadmium Compounds / Q000633:toxicity*; D016000:Cluster Analysis; D016207:Cytokines / Q000378:metabolism; D020022:Genetic Predisposition to Disease; D005978:Glutathione / Q000378:metabolism; D040941:Heredity; D008168:Lung / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D008297:Male; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D020556:Neutrophil Infiltration / Q000187:drug effects; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology; D010641:Phenotype; D011014:Pneumonia / Q000139:chemically induced* / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D045663:Quantum Dots / Q000633:toxicity*; D012307:Risk Factors; D018036:Selenium Compounds / Q000633:toxicity*; D013045:Species Specificity; D013440:Sulfides / Q000633:toxicity*; D013997:Time Factors; D017967:Zinc Compounds / Q000633:toxicity*
chemical_list: D019187:Cadmium Compounds; D016207:Cytokines; D018036:Selenium Compounds; D013440:Sulfides; D017967:Zinc Compounds; C058667:cadmium selenide; D005978:Glutathione; C031238:zinc sulfide
keywords: Collaborative Cross mouse strains; Genetics; Heritability; Lung inflammation; Quantum dots