Genotoxic effects of carbon nanotubes on human lung cells

Nanotechnology is a growing industry bringing with the increasing utilization of nanoparticles (NP). NPs are defined as particles with at least one dimension being smaller than 100 nm. They are an increasing concern because of their size and unique physico-chemical properties, but the knowledge of impact on human health is limited so far. One class of NPs that has raised special concern is carbon nanotubes (CNTs). CNTs are high aspect ratio allotropes of carbon that are used to produce several manufactured nanomaterials (MNM). They possess many attractive features and potential for widespread applications with workplace and subsequent public exposure. CNTs structural similarities to asbestos fibers have raised concern that they may pose a comparable health hazard. Chronic inflammation following inhalation of fiber-like compounds like asbestos are known to lead to several adverse effects such as fibrosis and cancer and the same may hold true for CNTs. This study was carried out to evaluate the genotoxic and inflammatory potential of CNTs on human lung cells. Crocidolite asbestos was included as a reference material to be able to directly compare effects between CNT and asbestos. Endpoints evaluated includes cytotoxicity, and expression of the pro-inflammatory mediators Interleukin-1 alpha (IL-1α), Interleukin-1 beta (IL-1β), Tumor necrosis factor-alpha (TNF-α) and Tumor protein 53 (TP53). Protein levels of Extracellular signal-regulated kinase (ERK) were also investigated. In addition we investigated the effects of CNTs on intercellular communication. The cytotoxicity results showed a clear dose dependent toxicity from both CNTs, and both were more toxic than asbestos. TNF-α was the only cytokine examined that showed upregulation of its mRNA levels after CNT exposure. Small changes were seen in ERK expression. Regarding effects of CNTs on cell to cell communication, levels of the gap junction gene Connexin 43 (Cx43) were downregulated at both mRNA and protein level. The intercellular communication was also shown inhibited by the use of the scrape loading assay. These are novel findings that point towards possible down regulation of gap junctions via Cx43 after CNT exposure