Fullerene (C60) Is Negative in the In Vivo Pig-A Gene Mutation Assay

Carbon nanoparticles, such as carbon nanotubes and fullerene (C60), are potential candidates as leading substances in nanotechnological fields, but little is known about their safety. Here we examined in vivo genotoxicity of C60, by performing the Pig-A gene mutation assay in the peripheral blood of male C57BL/6Cr mice. Mice were given single intraperitoneal injection of 3 mg of C60 particles in 0.5 mL suspension containing 0.1%-Tween80-saline. As a positive control for the Pig-A gene mutation assay, mice were given a single oral administration of N-nitroso-N-ethylurea. At 2 and 8 weeks after treatments, we analyzed CD24-negative and -positive red blood cells in peripheral blood and calculated Pig-A mutant frequencies. As a result, we detected no significant differences in the mutant frequencies between C60 treated and non-treated mice, indicating that C60 is negative for genotoxicity in vivo in the limited target tissues assessed in this study. For the full assessment, we need comprehensive whole body survey on the genotoxicity of C60.

[1]  B. Bay,et al.  Nanoparticle-induced pulmonary toxicity , 2010, Experimental biology and medicine.

[2]  Kyunghee Choi,et al.  Carbon fullerenes (C60s) can induce inflammatory responses in the lung of mice. , 2010, Toxicology and applied pharmacology.

[3]  Shigehisa Endoh,et al.  In vitro and in vivo genotoxicity tests on fullerene C60 nanoparticles. , 2009, Toxicology letters.

[4]  Takehiko Nohmi,et al.  Genotoxicity of nano/microparticles in in vitro micronuclei, in vivo comet and mutation assay systems , 2009, Particle and Fibre Toxicology.

[5]  S. Doak,et al.  NanoGenotoxicology: the DNA damaging potential of engineered nanomaterials. , 2009, Biomaterials.

[6]  R. Heflich,et al.  Accumulation and persistence of Pig-A mutant peripheral red blood cells following treatment of rats with single and split doses of N-ethyl-N-nitrosourea. , 2009, Mutation research.

[7]  R. Mittelstaedt,et al.  Evaluation of Macaca mulatta as a model for genotoxicity studies. , 2009, Mutation research.

[8]  Akihiko Hirose,et al.  Induction of mesothelioma by a single intrascrotal administration of multi-wall carbon nanotube in intact male Fischer 344 rats. , 2009, The Journal of toxicological sciences.

[9]  J. Bemis,et al.  Erythrocyte-based Pig-a gene mutation assay: demonstration of cross-species potential. , 2008, Mutation research.

[10]  Y. Katsuura,et al.  Development of an in vivo gene mutation assay using the endogenous Pig‐A gene: I. Flow cytometric detection of CD59‐negative peripheral red blood cells and CD48‐negative spleen T‐cells from the rat , 2008, Environmental and molecular mutagenesis.

[11]  R. Mittelstaedt,et al.  Development of an in vivo gene mutation assay using the endogenous Pig‐A gene: II. Selection of Pig‐A mutant rat spleen T‐cells with proaerolysin and sequencing Pig‐A cDNA from the mutants , 2008, Environmental and molecular mutagenesis.

[12]  Z. Marković,et al.  Biomedical potential of the reactive oxygen species generation and quenching by fullerenes (C60). , 2008, Biomaterials.

[13]  J. Kanno,et al.  Induction of mesothelioma in p53+/- mouse by intraperitoneal application of multi-wall carbon nanotube. , 2008, The Journal of toxicological sciences.

[14]  S. Piantadosi,et al.  PIG-A mutations in normal hematopoiesis. , 2004, Blood.

[15]  V. Rosti,et al.  X inactivation and somatic cell selection rescue female mice carrying a Piga-null mutation. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[16]  Teizo Fujita,et al.  Deficiency of the GPI anchor caused by a somatic mutation of the PIG-A gene in paroxysmal nocturnal hemoglobinuria , 1993, Cell.