First Steps Towards an Understanding of a Mode ofCarcinogenic Action for Vanadium Pentoxide |
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| Authors: | Schuler Detlef Chevalier Hans-Jörg Merker Mandy Morgenthal Katja Ravanat Jean-Luc Sagelsdorff Peter Walter Marc Weber Klaus McGregor Douglas |
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| Institution: | 1. Harlan Laboratories Ltd., Wölferstrasse 4, 4414 Füllinsdorf, Switzerland;2. AnaPath GmbH, Buchsweg 56, 4625 Oberbuchsiten, Switzerland;3. Harlan Cytotest Cell Research GmbH, In den Leppsteinswiesen 19, 64380 Rossdorf, Germany;4. CEA-Grenoble, INAC/SCIB/LAN 17 rue des Martyrs, 38054 Grenoble Cédex 9, France;5. TEC, 38 Shore Rd., Aberdour KY3 0TU, UK |
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| 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/m3), 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/m3, 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/m3. At 1 and
4?mg/m3, 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. |
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| Keywords: | comet assay DNA lesions mouse inhalation oxidative stress vanadium pentoxide |
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