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

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/m³). 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).