Absence of in vivo mutagenicity of multi-walled carbon nanotubes in single intratracheal instillation study using F344 gpt delta rats

Katsuyoshi Horibata,Dai Nakae,Katsuhiro Yuzawa,Akio Ogata,Masamitsu Honma,Akiko Ukai,Hiroshi Ando,Akemichi Nagasawa,Yoshikazu Kubo

doi:10.1186/s41021-016-0065-5

Abstract

IntroductionIt is known that fibrous particles of micrometer length, such as carbon nanotubes, which have same dimensions as asbestos, are carcinogenic. Carcinogenicity of nanomaterials is strongly related to inflammatory reactions; however, the genotoxicity mechanism(s) is unclear. Indeed, inconsistent results on genotoxicity of multi-walled carbon nanotubes (MWCNTs) have been shown in several reports. Therefore, we analyzed the in vivo genotoxicity induced by an intratracheal instillation of straight MWCNTs in rats using a different test system—the Pig-a gene mutation assay—that can reflect the genotoxicity occurring in the bone marrow. Since lungs were directly exposed to MWCNTs upon intratracheal instillation, we also performed the gpt assay using the lungs.FindingsWe detected no significant differences in Pig-a mutant frequencies (MFs) between the MWCNT-treated and control rats. Additionally, we detected no significant differences in gpt MFs in the lung between the MWCNT-treated and control rats.ConclusionsOur findings indicated that a single intratracheal instillation of MWCNTs was non-mutagenic to both the bone marrow and lung of rats.

Highlights

It is known that fibrous particles of micrometer length, such as carbon nanotubes, which have same dimensions as asbestos, are carcinogenic
Our findings indicated that a single intratracheal instillation of multiwalled carbon nanotubes (MWCNTs) was non-mutagenic to both the bone marrow and lung of rats
Pig-a assay Compared with the control, the Pig-a Mutant frequency (MF) clearly increased in the ENU- and ENU plus MWCNT-treated rats (Fig. 1)

Summary

Introduction

It is known that fibrous particles of micrometer length, such as carbon nanotubes, which have same dimensions as asbestos, are carcinogenic. In vivo comet assay revealed that a single intratracheal or pharyngeal instillation of MWCNTs to mice both induced DNA damage in the lungs in a dose-dependent manner [13, 15]. Another group reported that MWCNTs administered by gavage showed no genotoxic effect in an in vivo micronucleus test [12]. Horibata et al Genes and Environment (2017) 39:4 an intratracheal instillation of MWCNTs to rats was non-genotoxic, as demonstrated by the comet assay of the lung [14]. It was reported that an intratracheal instillation of MWCNTs in mice increased the mutation frequency detected by the gpt assay in the lung [13]

Methods

Results

Conclusion