A study on metabolic pathway of fullerene C60 in vivo.

• Project/Area Number: 23710083
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Risk sciences of radiation/Chemicals
• Research Institution: National Institute of Health Sciences
• Principal Investigator: KUBOTA Reiji 国立医薬品食品衛生研究所, 生活衛生化学部, 主任研究官 (80392299)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2011: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: フラーレン / 代謝物 / LC/MS/MS / in vitro / 細胞毒性 / 肝ミクロゾーム / 酸化物 / 一斉分析法 / ＬＣ-ＭＳ/ＭＳ / 水酸化物 / LC-MS/MS

Research Abstract

For the determination of fullerene derivative (C60O, C60O2, C60O3, and C60(OH) 2) with the possibility of existing as a metabolite of C60 in vivo, a sensitive analytical method using high performance liquid chromatography – tandem mass spectrometry (LC/MS/MS) and extraction procedure from samples of in vitro studies was established in this study. We examined the cytotoxic effects of fullerene derivative with HepG2 cells. C60O induced cytotoxic effects in HepG2 cells and the tendency was enhanced in a concentration–dependent manner. On the other hand, C60O2 and C60O3 were less toxic than C60. We evaluated the metabolism of fullerene in vitro by using rat liver microsomes. No fullerene derivatives were observed in this metabolic testing system.

Research Products

• [Journal Article] Sub-acute oral toxicity study with fullerene C60 in rats (2012)
  • Author(s): Takahashi, M., Kato, H., Doi, Y., Hagiwara, A., Hirata-Koizumi, M., Ono, A., Kubota, R., Nishimura, T., Hirose, A.
  • Journal Title: The Journal of Toxicological Sciences Volume: 37, 2 April Pages: 353-361
  • NAID: 10030126828
• [Journal Article] Time-dependent variation in the biodistribution of C60 in rats determined by liquid chromatography-tandem mass spectrometry (2011)
  • Author(s): Kubota, R., Tahara, M., Shimizu, K., Sugimoto, N., Hirose, A., Nishimura T.
  • Journal Title: Toxicology Letters Volume: 206 Pages: 172-177
• [Presentation] Bio-distribution of fullerenes intravenous administration in rat (2011)
  • Author(s): Nishimura, T., Kubota, R., Tahara, M., Shimizu, K., Obama, T., Sugimoto, N., Hirose, A.
  • Organizer: 50th Anniversary Annual Meeting & ToxExpo, abstracts
  • Place of Presentation: SOT, Washington, D.C., USA
• [Presentation] Time-dependent biodistribution of C60 in rat after tail-vein administration (2011)
  • Author(s): Kubota, R., Tahara, M., Shimizu, K., Kobayashi, N., Sugimoto, N., Hirose, A., Nishimura T.
  • Organizer: 47th Congress of the European Societies of Toxicology, abstracts.
  • Place of Presentation: Paris, France(2342)
• [Presentation] Bio-distribution of C60 fullerene injected into the rat tail vein (2011)
  • Author(s): Nishimura, T., Kubota, R., Tahara, M., Shimizu, K., Obama, T., Hirose, A., Sugimoto, N.
  • Organizer: 5th International Symposium on Nanotechnology, Occupational and Environmental Health (NanOEH)
  • Place of Presentation: Boston, USA(abstracts)
• [Presentation] Tissue distribution of fullerene after injected into rat tail vein to mimic the absorption from the digestive tract (2010)
  • Author(s): Nishimura, T., Kubota, R., Shimizu, K., Tahara, M., Obama, T., Sugimoto, N., Kanno, J., Hirose, A.
  • Organizer: XII International Congress of Toxicology, abstracts. P303-024
  • Place of Presentation: Barcelona, Spain
• [Presentation] Bio-distribution of fullerenes intravenous administration (2010)
  • Author(s): Nishimura, T., Kubota, R., Tahara, M., Shimizu, K., Obama, T., Sugimoto, N., Hirose, A., Ikarashi, Y.
  • Organizer: 2010 Annual Meeting of the Korea Society of Environmental Health and Toxicology, abstracts
  • Place of Presentation: Suwon, Korea