Induction of mesothelioma in p53+/- mouse by intraperitoneal application of multi-wall carbon nanotubes
|This study reported that p53 heterozygous mice developed and died from peritoneal mesothelioma approximately 144 days following a single intraperitoneal injection of multiwalled carbon nanotubes (MWCNT) but not after treatment with fullerenes. The authors concluded that it would be prudent to implement strategies to keep good control of exposure to fibrous or rod-shaped carbon materials in the workplace until the biological properties and carcinogenic potential are fully assessed. However, it is important to note that the route of administration was intraperitoneal and not inhalation and the mouse model used is susceptible to the development of tumors.|
Reviewed by Annette Santamaria, PhD, MPH, DABT. ENVIRON International Corporation.
- Takagi et al. 2008. Induction of mesothelioma in p53+/- mouse by intraperitoneal application of multi-wall carbon nanotubes. J. Tox. Sci. 33(1):105-116. DOI: 10.2131/jts.33.105
Concern has been expressed in the scientific and regulatory communities about the potential for the induction of pulmonary toxicity following inhalation exposure to carbon nanotubes. The potential similarity in size and shape between carbon nanotubes and asbestos fibers has led to some concern that there may be potential respiratory health risks associated with workplace and environmental exposure to CNT because the high aspect ratio of carbon nanotubes is physically similar to the high aspect ratio of asbestos.
This study was conducted to evaluate the effects of an intraperitoneal (i.p.) injection of MWCNT compared to i.p. injections of fullerenes or crocidolite in mice heterozygous for the p53 gene. This mouse model has been shown to be susceptible to the development of tumors from a variety of chemical agents and has been used to screen for potential carcinogens, including asbestos.
Heterozygous p53+/- mice (19 per group) were treated with a single dose (3 mg/ml) of MWCNT, fullerenes, or crocidolite and observed for 25 weeks (through day 180). C57BL/6 mice were similarly treated and sacrificed at day 10 for the observation of early peritoneal responses. Visceral organs including the liver, kidney, spleen, digestive tract and macroscopic tumors were fixed in formalin, and paraffin-embedded sections were stained with H&E and examined histologically by light microscopy.
The C57BL/6 mice in the satellite group showed slight fibrinous adhesions with a trace amount of ascites with scattered black spots of MWCNT aggregates at 10 days. The mice treated with crocidolite had similar responses but to a lesser extent, and the fullerene group showed minimal changes except for the black spots of aggregates on the serosal surfaces. Takagi et al. (2008) reported the development of fibrotic deposits, adhesions in the intestines, and granulomas in the p53 heterozygous mice and the development of mesotheliomas in the peritoneum approximately 144 days after treatment with MWCNT. The overall incidence of peritoneal mesothelioma after the first incidental case found in the MWCNT group at day 84 was 14/16 (87.5%). The crocidolite-treated mice showed similar responses but to a lesser extent and the overall incidence of peritoneal mesothelioma was 14/18 (77%). The fullerene treated group did not have any peritoneal adhesions, fibrous thickening, or tumors; only small black plaques scattered on the serosal surface of the lungs.
The authors concluded that it would be prudent to implement strategies to keep good control of exposure to fibrous or rod-shaped carbon materials in the workplace until the biological properties and carcinogenic potential are fully assessed. However, it is important to note that the route of administration was intraperitoneal and not inhalation and the mouse model used is susceptible to the development of tumors.
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