Chronic inhalation of
vanadium pentoxide (
V2O5) increases the incidence of alveolar/bronchiolar
tumors in male and female B6C3F1 mice at 1, 2, or 4 mg/m(3). The genotoxicity of
V2O5 has been extensively investigated in the literature with mixed results. In general, tests for gene mutations have been negative. Both positive and negative results were reported for clastogenicity in vitro with some reports suggesting aneugenic potential. In vivo,
V2O5 was negative in the mouse micronucleus test (erythrocyte) and comet assay (lung). Previously, K-ras mutations have been detected in the lung
tumors in mice exposed to
V2O5. Recently, a short-term inhalation study in B6C3F1 mice reported slight induction of
8-oxodGuo DNA lesions in lungs. Because
8-oxodGuo DNA lesions can lead to gene mutations if not repaired or if misrepaired, we have used groups of transgenic Big Blue (BB) mice (B6C3F1) to test whether
V2O5 has mutagenic potential in vivo in the
tumor target tissue under the conditions of the bioassay. Groups of six male BB mice were exposed to particulate
aerosols containing 0, 0.1, or 1 mg/m(3) (tumorigenic concentration)
V2O5 for 4 or 8 weeks (6h/day, 5 days/week) and cII mutant frequencies (MFs) were evaluated in the right lungs. A significant increase in lung weight was noted in mice exposed to 1 mg/m(3)
V2O5 (P ≤ 0.05) compared to
sham control, confirming exposure to an inflammatory level of the test material. The mean MFs (× 10(-6)) of mice in the 4-week exposure groups were 30 (
sham control), 39 (0.1 mg/m(3)), and 24 (1 mg/m(3)) while the corresponding values in the 8-week exposure groups were 29, 48, and 17, respectively. None of these cII MFs measured at any time point was significantly higher than the corresponding control MFs (P ≥ 0.1). Overall, these results suggest that mutagenicity is not likely to be an initial key event in the lung tumorigenicity of
V2O5.