Abstract 3604: Evaluation of carcinogenic effect of multiwall carbon nanotubes on the rat lung at 2 and 52 weeks after pulmonary instillation.

Abstract

Abstract Multiwall carbon nanotubes (MWCNT) have recently been shown to contain fibers similar to asbestos in length and diameter. When these fibers are inhaled, MWCNT can induce pulmonary toxicity including inflammation, granuloma, fibrosis, and hyperplasia. Also, a characteristic shared with asbestos fibers has led to concern that environmental or occupational exposure to MWCNT might cause asbestos-like pulmonary diseases including carcinoma. To examine MWCNT's pulmonary toxicity, we used the intrapulmonary spraying (IPS) technique. Also, to examine the effects depending on its length of MWCNT, using a 25 μm-sieve it was separated into three fractions; the remaining (R), flow through (FT), and whole (W). Male F344 rats were treated with 0.5 mL of 250 mg/mL suspensions of each fraction of MWCNT eight times over a 14-day period by intrapulmonary spraying. Six hours after the last IPS, the rats were sacrificed and complete autopsy was done (short-term exp). Mean length of MWCNT was 2.6 μm (FT) and 4.2 μm (W). Length of the R fraction could not be measured because of its tangled up status. At 52 weeks after the start of the experiment, the remaining rats were sacrificed and complete autopsy was also done using a 25 μm-sieve. In the short-term exp, MWCNT were found mainly in focal granulomatous lesions in the alveoli and in alveolar macrophages. MWCNT were also seen in the mediastinal lymph nodes. Inflammatory cell infiltration and granuloma formation were seen in each fraction treatment group. Mean area of inflammatory cell infiltration was significantly increased in the FT fraction treatment group as compared to the other two fractions treatment groups and control group. In the long-term exp, MWCNT were detected in focal granulomatous/fibrous lesions in the alveoli and in alveolar macrophages. In the lung tissue of each fraction treatment group, mean area of granulomatous/fibrous lesions increased compared to the control group. In the lung tissue of the short-term exp, the levels of mRNA/protein expression of Csf3, IL6, Cxcl2, and Ccl4, which were highly expressed in a microarray analysis in primary cultured macrophages, were enhanced in each fraction treatment group compared to the control group. In the long-term exp, the levels of mRNA expression of Csf3 and IL6 were markedly low. mRNA expression of Cxcl2 and Ccl4 were almost same level as the control. IPS of MWCNT did not cause tumors in alveolar epithelial tissues. These results indicate that MWCNT cause inflammatory toxic effects on the rat lung at 2 and 52 weeks after instillation. The initial hypothesis of a carcinogenic activity of instilled MWCNT could not be verified in a 52-week bioassay system. Citation Format: Masumi Suzui, Takamasa Numano, Mitsuru Futakuchi, Katsumi Fukamachi. Evaluation of carcinogenic effect of multiwall carbon nanotubes on the rat lung at 2 and 52 weeks after pulmonary instillation. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3604. doi:10.1158/1538-7445.AM2013-3604