Evaluation of cII mutations in lung of male Big Blue mice exposed by inhalation to vanadium pentoxide for up to 8 weeks

Publication date: Available online 29 June 2015 Source:Mutation Research/Genetic Toxicology and Environmental Mutagenesis Author(s): Mugimane G. Manjanatha , Sharon D. Shelton , Lynne Haber , Bhaskar Gollapudi , Judith A. MacGregor , Narayanan Rajendran , Martha M. Moore Chronic inhalation of vanadium pentoxide (V2O5) increases the incidence of alveolar/bronchiolar tumors in male and female B6C3F1 mice at 1, 2 or 4mg/m3. 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 1mg/m3 (tumorigenic concentration) V2O5 for 4 or 8 weeks (6hours/day, 5 days/week) and cII mutant frequencies (MFs) were ev...
Source: Mutation Research Genetic Toxicology and Environmental Mutagenesis - Category: Genetics & Stem Cells Source Type: research