title: First Steps Towards an Understanding of a Mode ofCarcinogenic Action for Vanadium Pentoxide.
abstract: Inhalation of vanadium pentoxide clearly increases the incidence of alveolar/bronchiolar neoplasms in male and female B6C3F1 mice at all concentrations tested (1, 2 or 4 mg/m(3)), whereas responses in F344/N rats was, at most, ambiguous. While vanadium pentoxide is mutagenic in vitro and possibly in vivo in mice, this does not explain the species or site specificity of the neoplastic response. A nose-only inhalation study was conducted in female B6C3F1 mice (0, 0.25, 1 and 4 mg/m(3), 6 h/day for 16 days) to explore histopathological, biochemical (α-tocopherol, glutathione and F2-isoprostane) and genetic (comet assays and 9 specific DNA-oxo-adducts) changes in the lungs. No treatment related histopathology was observed at 0.25 mg/m(3). At 1 and 4 mg/m(3), exposure-dependent increases were observed in lung weight, alveolar histiocytosis, sub-acute alveolitis and/or granulocytic infiltration and a generally time-dependent increased cell proliferation rate of histiocytes. Glutathione was slightly increased, whereas there were no consistent changes in α-tocopherol or 8-isoprostane F2α. There was no evidence for DNA strand breakage in lung or BAL cells, but there was an increase in 8-oxodGuo DNA lesions that could have been due to vanadium pentoxide induction of the lesions or inhibition of repair of spontaneous lesions. Thus, earlier reports of histopathological changes in the lungs after inhalation of vanadium pentoxide were confirmed, but no evidence has yet emerged for a genotoxic mode of action. Evidence is weak for oxidative stress playing any role in lung carcinogenesis at the lowest effective concentrations of vanadium pentoxide.
authors.forename: Detlef
authors.initials: D
authors.lastname: Schuler
authors.forename: Hans-Jörg
authors.initials: HJ
authors.lastname: Chevalier
authors.forename: Mandy
authors.initials: M
authors.lastname: Merker
authors.forename: Katja
authors.initials: K
authors.lastname: Morgenthal
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Ravanat
authors.forename: Peter
authors.initials: P
authors.lastname: Sagelsdorff
authors.forename: Marc
authors.initials: M
authors.lastname: Walter
authors.forename: Klaus
authors.initials: K
authors.lastname: Weber
authors.forename: Douglas
authors.initials: D
authors.lastname: McGregor