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).