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Dose-dependent mesothelioma induction by intraperitoneal administration of multi-wall carbon nanotubes in p53 heterozygous mice.

Takagi A, Hirose A, Futakuchi M, Tsuda H, Kanno J - Cancer Sci. (2012)

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.

View Article: PubMed Central - PubMed

Affiliation: Division of Cellular and Molecular Toxicology, Biological Safety Research Center, National Institute of Health Sciences, Tokyo, Japan.

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Dose-dependent induction of mesotheliomas by micrometer-sized multi-wall carbon nanotubes (μm-mwcnt). Mice with lethal mesotheliomas are plotted using the Kaplan–Meier method. High: 300 μg/mouse, corresponding to 1 × 108 fibers/mouse; middle: 30 μg/mouse, corresponding to 1 × 107 fibers/mouse; low: 3 μg/mouse, corresponding to 1 × 106 fibers/mouse); previous: data from a previous study (i.e. 3 mg/mouse, corresponding to 1 × 109 fibers/mouse). No mesothelioma was observed in the vehicle control group.
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fig01: Dose-dependent induction of mesotheliomas by micrometer-sized multi-wall carbon nanotubes (μm-mwcnt). Mice with lethal mesotheliomas are plotted using the Kaplan–Meier method. High: 300 μg/mouse, corresponding to 1 × 108 fibers/mouse; middle: 30 μg/mouse, corresponding to 1 × 107 fibers/mouse; low: 3 μg/mouse, corresponding to 1 × 106 fibers/mouse); previous: data from a previous study (i.e. 3 mg/mouse, corresponding to 1 × 109 fibers/mouse). No mesothelioma was observed in the vehicle control group.

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


Dose-dependent mesothelioma induction by intraperitoneal administration of multi-wall carbon nanotubes in p53 heterozygous mice.

Takagi A, Hirose A, Futakuchi M, Tsuda H, Kanno J - Cancer Sci. (2012)

Dose-dependent induction of mesotheliomas by micrometer-sized multi-wall carbon nanotubes (μm-mwcnt). Mice with lethal mesotheliomas are plotted using the Kaplan–Meier method. High: 300 μg/mouse, corresponding to 1 × 108 fibers/mouse; middle: 30 μg/mouse, corresponding to 1 × 107 fibers/mouse; low: 3 μg/mouse, corresponding to 1 × 106 fibers/mouse); previous: data from a previous study (i.e. 3 mg/mouse, corresponding to 1 × 109 fibers/mouse). No mesothelioma was observed in the vehicle control group.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3569866&req=5

fig01: Dose-dependent induction of mesotheliomas by micrometer-sized multi-wall carbon nanotubes (μm-mwcnt). Mice with lethal mesotheliomas are plotted using the Kaplan–Meier method. High: 300 μg/mouse, corresponding to 1 × 108 fibers/mouse; middle: 30 μg/mouse, corresponding to 1 × 107 fibers/mouse; low: 3 μg/mouse, corresponding to 1 × 106 fibers/mouse); previous: data from a previous study (i.e. 3 mg/mouse, corresponding to 1 × 109 fibers/mouse). No mesothelioma was observed in the vehicle control group.
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

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.

View Article: PubMed Central - PubMed

Affiliation: Division of Cellular and Molecular Toxicology, Biological Safety Research Center, National Institute of Health Sciences, Tokyo, Japan.

Show MeSH
Related in: MedlinePlus