title: Hepatic and pulmonary toxicogenomic profiles in mice intratracheally instilled with carbon black nanoparticles reveal pulmonary inflammation, acute phase response, and alterations in lipid homeostasis.
abstract: Global pulmonary and hepatic messenger RNA profiles in adult female C57BL/6 mice intratracheally instilled with carbon black nanoparticles (NPs) (Printex 90) were analyzed to identify biological perturbations underlying systemic responses to NP exposure. Tissue gene expression changes were profiled 1, 3, and 28 days following exposure to 0.018, 0.054, and 0.162 mg Printex 90 alongside controls. Pulmonary response was marked by increased expression of inflammatory markers and acute phase response (APR) genes that persisted to day 28 at the highest exposure dose. Genes in the 3-hydroxy-3-methylglutaryl-Coenzyme A (HMG-CoA) reductase pathway were increased, and those involved in cholesterol efflux were decreased at least at the highest dose on days 1 and 3. Hepatic responses mainly consisted of the HMG-CoA reductase pathway on days 1 (high dose) and 28 (all doses). Protein analysis in tissues and plasma of 0.162 mg Printex 90-exposed mice relative to control revealed an increase in plasma serum amyloid A on days 1 and 28 (p < 0.05), decreases in plasma high-density lipoprotein on days 3 and 28, an increase in plasma low-density lipoprotein on day 28 (p < 0.05), and marginal increases in total hepatic cholesterol on day 28 (p = 0.06). The observed changes are linked to APR. Although further research is needed to establish links between observations and the onset and progression of systemic disorders, the present study demonstrates the ability of NPs to induce systemic effects.
authors.affiliation: Environmental Health Sciences and Research Bureau, Mechanistic Studies Division, Health Canada, Ottawa, Canada, K1A 0K9.
authors.forename: Julie A
authors.initials: JA
authors.lastname: Bourdon
authors.forename: Sabina
authors.initials: S
authors.lastname: Halappanavar
authors.forename: Anne T
authors.initials: AT
authors.lastname: Saber
authors.forename: Nicklas R
authors.initials: NR
authors.lastname: Jacobsen
authors.forename: Andrew
authors.initials: A
authors.lastname: Williams
authors.forename: Håkan
authors.initials: H
authors.lastname: Wallin
authors.forename: Ulla
authors.initials: U
authors.lastname: Vogel
authors.forename: Carole L
authors.initials: CL
authors.lastname: Yauk
mesh_terms: D000210:Acute-Phase Reaction / Q000139:chemically induced* / Q000235:genetics / Q000276:immunology; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D002784:Cholesterol / Q000097:blood; D016207:Cytokines / Q000097:blood / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D006706:Homeostasis; D018836:Inflammation Mediators / Q000097:blood; D007442:Intubation, Intratracheal; D050356:Lipid Metabolism / Q000187:drug effects* / Q000235:genetics; D008099:Liver / Q000187:drug effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D053758:Nanoparticles; D020411:Oligonucleotide Array Sequence Analysis; D011014:Pneumonia / Q000139:chemically induced* / Q000235:genetics / Q000276:immunology; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D053260:Soot / Q000633:toxicity*; D013997:Time Factors; D043922:Toxicogenetics / Q000379:methods
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D012333:RNA, Messenger; D053260:Soot; D002784:Cholesterol