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Mutagenesis by asbestos in the lung of λ-lacI transgenic rats

Authors
Journal
Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis
0027-5107
Publisher
Elsevier
Publication Date
Volume
553
Identifiers
DOI: 10.1016/j.mrfmmm.2004.06.023
Keywords
  • Asbestos
  • Inflammation
  • Mutations
  • Transgenic Rats

Abstract

Abstract In order to get more insight into the mechanism of asbestos-related lung cancer, the mutagenic potential of asbestos was examined in vivo in rat lung. Groups of five transgenic λ-lacI (Big Blue™) rats were intratracheally instilled with single doses of 1 or 2 mg, or with four weekly doses of 2 mg, per animal of the amosite asbestos. Sixteen weeks after instillation, the mutation frequency was found to be increased in lung DNA by 2-fold at doses of 2 mg ( P = 0.035) and of 4 × 2 mg ( P = 0.007) amosite. No significant changes were observed after 4 weeks of exposure. In separate experiments, wild-type F344 rats were treated by the same regimen as described above and markers of inflammation, genotoxicity, cell proliferation and lung tissue damage were analysed. Our results indicate a weak but persistent inflammation and cell proliferation which possibly plays a major role in the observed mutagenic effect.

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