title: Using gene expression profiling to evaluate cellular responses in mouse lungs exposed to V2O5 and a group of other mouse lung tumorigens and non-tumorigens.
abstract: Many compounds test positive for lung tumors in two-year NTP carcinogenicity bioassays in B6C3F1 mice. V2O5 was identified as a lung carcinogen in this assay, leading to its IARC (International Agency for Research on Cancer) classification as group 2b or a "possible" human carcinogen. To assess potential tumorigenic mode of action of V2O5, we compared gene expression and gene ontology enrichment in lung tissue of female B6C3F1 mice exposed for 13 weeks to a V2O5 particulate aerosol at a tumorigenic level (2.0 mg/m(3)). Relative to 12 other compounds also tested for carcinogenicity in 2-year bioassays in mice, there were 1026 differentially expressed genes with V2O5, of which 483 were unique to V2O5. Ontology analysis of the 1026 V2O5 differentially expressed genes showed enrichment for hyaluronan and sphingolipid metabolism, adenylate cyclase functions, c-AMP signaling and PKA activation/signaling. Enrichment of lipids/lipoprotein metabolism and inflammatory pathways were consistent with previously reported clinical findings. Enrichment of c-AMP and PKA signaling pathways may arise due to inhibition of phosphatases, a known biological action of vanadate. We saw no enrichment for DNA-damage, oxidative stress, cell cycle, or apoptosis pathway signaling in mouse lungs exposed to V2O5 which is in contrast with past studies evaluating in vivo gene expression in target tissues of other carcinogens (arsenic, formaldehyde, naphthalene and chloroprene).
authors.affiliation: The Hamner Institutes for Health Sciences, Six Davis Drive, PO Box 12137, Research Triangle Park, NC 27709, USA. Electronic address: mblack@thehamner.org.
authors.forename: Michael B
authors.initials: MB
authors.lastname: Black
authors.affiliation: The Hamner Institutes for Health Sciences, Six Davis Drive, PO Box 12137, Research Triangle Park, NC 27709, USA. Electronic address: Darol.Dodd@crl.com.
authors.forename: Darol E
authors.initials: DE
authors.lastname: Dodd
authors.affiliation: The Hamner Institutes for Health Sciences, Six Davis Drive, PO Box 12137, Research Triangle Park, NC 27709, USA. Electronic address: pmcmullen@thehamner.org.
authors.forename: Patrick D
authors.initials: PD
authors.lastname: McMullen
authors.affiliation: The Hamner Institutes for Health Sciences, Six Davis Drive, PO Box 12137, Research Triangle Park, NC 27709, USA. Electronic address: spendse@thehamner.org.
authors.forename: Salil
authors.initials: S
authors.lastname: Pendse
authors.affiliation: Toxicology Consulting Services, 26881 Wedgewood Dr., Bonita Springs, FL 34134, USA. Electronic address: jamacgregor101@gmail.com.
authors.forename: Judith A
authors.initials: JA
authors.lastname: MacGregor
authors.affiliation: Exponent Inc., 1910 St. Andrews St., Midland, MI 48640, USA. Electronic address: bgollapudi@exponent.com.
authors.forename: B Bhaskar
authors.initials: BB
authors.lastname: Gollapudi
authors.affiliation: The Hamner Institutes for Health Sciences, Six Davis Drive, PO Box 12137, Research Triangle Park, NC 27709, USA. Electronic address: mandersen@thehamner.org.
authors.forename: Melvin E
authors.initials: ME
authors.lastname: Andersen
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002273:Carcinogens / Q000633:toxicity*; D002453:Cell Cycle / Q000187:drug effects; D004249:DNA Damage / Q000187:drug effects; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D008168:Lung / Q000187:drug effects*; D008175:Lung Neoplasms / Q000139:chemically induced; D051379:Mice; D008815:Mice, Inbred Strains; D046228:Microarray Analysis / Q000379:methods; D018384:Oxidative Stress / Q000187:drug effects; D059467:Transcriptome / Q000187:drug effects*; D017968:Vanadium Compounds / Q000633:toxicity*
chemical_list: D002273:Carcinogens; D017968:Vanadium Compounds; C066075:vanadium pentoxide
keywords: Functional ontology; Gene expression; Mouse lung; Vanadium pentoxide