Analysis Of Size-Dependent Carcinogenic Potential Of Multiwalled Carbon Nanotubes

Akihiko HIROSE, National Institute of Health Sciences, Japan
SAKAMOTO Y. 2 , NISHIMAKI-MOGAMI T. 1 , TAQUAHASHI Y. 3 , YAMADA T. 1 , NISHIMURA T. 4 , INOMATA A. 2 , NAKAE D. 5 , TSUDA H. 6 , KANNO J. 3

1 Division of Risk Assessment, National Institute of Health Sciences, Tokyo, Japan
2 Department of Environmental Health and Toxicology, Tokyo Metropolitan. Institute of Public Health, Tokyo, Japan
3 Division of Cellular and Molecular Toxicology, National Institute of Health Sciences, Tokyo, Japan
4 Teikyo Heisei University, Tokyo, Japan
5 Department of Nutritional Science and Food Safety, Tokyo University of Agriculture, Tokyo, Japan
6 Nagoya City University, Nagoya, Japan

MWNT-7, a kind of the various types of multi-wall carbon nanotubes (MWCNTs) has the potential to induce mesothelioma by an intrascrotal or intraperitoneal administration in rats and mice. And a recently reported chronic two-year inhalation study indicated that the MWNT-7 induced lung cancer in rats. To investigated carcinogenic potential of other types of MWCNT, we exposed seven different MWCNTs to rat by single intraperitoneal administration and the rats were then housed for 52 weeks. The potentials of the cytokines induction by macrophage cell of THP-1 were examined for the MWCNTs. At the end of the observation period, four of the seven different MWCNTs induced mesothelioma in all rats of each administration group. The remaining three MWCNTs caused low incidence (0-7.7%) of mesothelioma. The relative carcinogenic potency seems to be depending on the ratios of longer (more than 5 μm) fiber numbers. The potency of the production of inflammatory cytokines (ex. IL-1β) in the THP-1 cells also mainly depended on the ratio of longer fibers numbers and correlated with the potency of the mesothelioma induction. However, in some types of MWCNTs, the cytokines induction potency was not correlated with the mesothelioma induction potency. We previously reported that the longer type (7.6 ± 4.5 μm) of high-temperature calcined fullerene nanowhiskers (HTCFNW) exhibited robust IL-1β production. However, at the preliminary study, the HTCFNW did not induce mesothelioma by single intraperitoneal administration in mice. In conclusion, bio-persistency for long-term and sample preparation methods at in vitro study may be an important factor to assess the carcinogenic potency by MWCNTs exposure, in addition to the ratio of long fiber numbers. This study was supported in part by Health and Labour Sciences Research Grants (H24-Kagaku-Shitei-009, H27-Kagaku-Shitei-004) from Ministry of Health, Labour and Welfare, Japan.