Dose-dependent mesothelioma induction by intraperitoneal administration of multi-wall carbon nanotubes in p53 heterozygous mice.
Bottom Line: Right beneath was a mononuclear cell accumulation consisting of CD45- or CD3-positive lymphocytes and CD45/CD3-negative F4/80 faintly positive macrophages; some of the macrophages contained singular MWCNT in their cytoplasm.The lesions were devoid of epithelioid cell granuloma and fibrosis.These findings were in favor of the widely proposed mode of action of fiber carcinogenesis, that is, frustrated phagocytosis where the mesotheliomagenic microenvironment on the peritoneal surface is neither qualitatively altered by the density of the fibers per area nor by the formation of granulomas against agglomerates.
Affiliation: Division of Cellular and Molecular Toxicology, Biological Safety Research Center, National Institute of Health Sciences, Tokyo, Japan.Show MeSH
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Mentions: Our first study identified the mesotheliomagenic potency of Mitsui MWCNT-7 at a single maximum dose (i.e. 109 fibers) in the peritoneal cavity of p53 heterozygous (p53+/−) mice2 (data shown as a reference in Fig 1). Marsella et al.9 has shown that development of mesothelioma by crocidolite asbestos was accelerated in this mutant mouse. We have bred this mouse and tested it as an alternative model to replace the wild-type mouse carcinogenicity test of the National Toxicology Program of the National Institute of Environmental Health Sciences/NIH of the United States.10 As a result, spontaneous neoplastic lesions of this model have been well characterized.11Figure 1
Affiliation: Division of Cellular and Molecular Toxicology, Biological Safety Research Center, National Institute of Health Sciences, Tokyo, Japan.