Single-walled carbon nanotubes: differential genotoxic potential associated with physico-chemical properties

Abstract

Single-walled carbon nanotubes (SWCNTs) have recently attracted great attention because of their fibrous structure and high aspect ratio. Here the genotoxic potential of 400-800 nm, 1-3 μm and 5-30 μm SWCNT with respect to their geometry and surface characteristics was studied. Following thorough physico-chemical characterisation, human bronchial epithelial (BEAS-2B) and lymphoblastoid (MCL-5) cells were treated with SWCNT for 24 or 48 h. This showed significant increases in micronucleus frequency in a time- and dose-dependent manner in both cell types in the absence of cytotoxicity. Over the same dose range, only 1-3 μm SWCNT gave rise to significant increases in hprt point mutations at doses ≥25 μg/ml. Cellular 2,7-dichlorodihydrofluoresceindiacetate (DCFH-DA) fluorescence assay and RT-PCR for oxidative pathway gene profiling revealed a possible oxidative mechanism for the genotoxicity observed in the 1-3 μm SWCNT. Consequently, this study has demonstrated that SWCNT genotoxicity is dependent on its secondary structure under experimental conditions and oxidative stress alone cannot account for the observed damage.

Evaluating the mechanistic evidence and key data gaps in assessing the potential carcinogenicity of carbon nanotubes and nanofibers in humans

“…Mutations in the HGPRT gene were increased in BEAS-2B cells after exposure to SWCNTs with a length of 1–5 μm, whereas shorter (0.4–0.8 μm) and longer (5–30 μm) SWCNTs were not associated with mutagenicity (Manshian et al 2013). Exposure to SWCNTs (0.5–2 μm) was associated with increased mutation frequency in the HGPRT gene in Chinese hamster V79 cells, whereas MWCNTs (0.5–2 μm) did not induce mutations (Mrakovcic et al 2015).…”

“…In addition, 13 out of 18 studies report increased micronuclei frequency in human cell lines after exposure to MWCNTs, including three independent studies of MWCNT-7 (Muller et al 2008a, 2008b; Asakura et al 2010; Cveticanin et al 2010; Migliore et al 2010; Di Giorgio et al 2011; Srivastava et al 2011; Kato et al 2013; Wu et al 2013; Darne et al 2014; Tavares et al 2014; Visalli et al 2015; Kim et al 2016); five studies showed null effects (Szendi & Varga 2008; Thurnherr et al 2011; Lindberg et al 2013; Ponti et al 2013; Mrakovcic et al 2015). Eight out of 13 studies report increased micronuclei frequency in human cell lines after exposure to either SWCNTs or MWCNTs (Cveticanin et al 2010; Migliore et al 2010; Cicchetti et al 2011; Di Giorgio et al 2011; Kisin et al 2011; Manshian et al 2013; Darne et al 2014; Kim & Yu 2014; Kim et al 2016); five studies showed null effects (Kisin et al 2007; Lindberg et al 2009; Lindberg et al 2013; Pelka et al 2013; Mrakovcic et al 2015). Null effect studies used CNTs similar to the CNTs that caused micronuclei formation with respect to diameter, length, specific surface area and purity, although it should be emphasized that many publications contain insufficient information on fiber characteristics.…”

“…Exposure to MWCNTs has been associated with increased frequency of micronuclei in lymphocytes (1–5 μm long, Cveticanin et al 2010), murine macrophage cell lines (RAW 264.7) (0.5–50 μm, Di Giorgio et al 2011) and human breast cancer epithelial cells (MCF-7) (700 nm, Muller et al 2008a). Another study showed increased micronuclei in BEAS-2B and immortalized human lymphoblastoid TK ± cells (MCL-5) cells after exposure to MWCNTs with short (400–800 nm), medium (1–3 μm) and long (5–30 μm) fiber length (Manshian et al 2013). A sample of MWCNTs with relatively short fiber length (0.7 μm) and low transition metal content (0.48% Fe and 0.49% Co) was used to study the impact of MWCNT structural defects and metals on the formation of micronuclei in rat lung epithelial cell lines (RLE cells) (Muller et al 2008b).…”

“…To summarize, mutagenesis in mammalian cells has been found negative, including one study of MWCNT-7 (Asakura et al 2010) and two studies of SWCNTs (Jacobsen et al 2008; Manshian et al 2013). Lack of mutagenetic activity in terms of frameshift and base pair substitutions has been shown following bacterial exposure to MWCNTs (Di Sotto et al 2009; Wirnitzer et al 2009; Kim et al 2011; Taylor et al 2014) and SWCNTs (Kisin et al 2007; Ema et al 2013a; Naya et al 2011; Kim et al 2015).…”

Faserstäube, anorganisch [MAK Value Documentation in German language, 2018]

“…Ein aktiver Internalisie rungsprozess erklärt jedoch das Vorliegen von membranumschlossenen intrazellulären Fasern, wie es in mehreren Studien beobachtet wird (Foldbjerg et al 2014;Guo et al 2011;Lindberg et al 2013;Manshian et al 2013;MonteiroRiviere et al 2005;Srivastava et al 2011).…”