Comparative analysis of lung and blood transcriptomes in mice exposed to multi-walled carbon nanotubes

Assessment of the Carcinogenicity of Carbon Nanotubes in the Respiratory System

“…However, since the last IARC evaluation of CNT carcinogenicity, conducted in 2014, when enough evidence was available only for Mitsui-7, nine new studies have been performed on humans exposed to CNTs in the workplace, documenting markers of fibrosis, profibrotic inflammatory mediators, and immune markers [ 21 , 34 , 35 , 94 ]; epigenetic changes in genes related to DNA repair, cell cycle and repression of transcription [ 22 ]; deregulation in pathways and signaling networks linked to pulmonary and carcinogenic outcomes [ 36 ]; increase of oxidative markers in the exhaled breath condensates [ 37 ], increase in mtDNA copy number [ 75 ]; and development of respiratory allergies [ 95 ]. Recent findings in vivo have clearly indicated that CNTs induce a sustained inflammatory response and oxidative stress, and fibrosis and histological alterations have been documented in animals exposed to MWCNTs ( Table 1 ) and SWCNTs ( Table 2 ) by inhalation, aspiration, and tracheal instillation [ 32 , 44 , 58 ]. The development of mesothelial hyperplasia, mesothelioma, and lung tumors have been also described with SWCNTs and long fibers of both asbestos and MWCNTs [ 32 , 38 , 46 , 59 ] ( Figure 2 ).…”

“…However, other studies in vivo have demonstrated that both long and short industrial MWCNTs induced granulomatous changes in the lungs, development of pulmonary fibrosis, and inflammation accompanied by increase in vimentin, TGF-beta, IL-1b, IL-18, and cardiac fibrotic deposition [ 40 , 41 , 42 , 43 , 44 ]. Commercial short MWCNTs (tangled) (Graphistrength© C100; Arkema, France) showed prolonged TNF-α release in BAL of exposed rats associated with increased collagen staining [ 45 ].…”

“…Few data are available regarding the characteristics grouped below. Available studies have demonstrated that CNTs can interact and activate the complement system, a key part of the immune system, and induce an early and sustained immunosuppressive response [44,[88][89][90]. Moreover, it has been shown that SWCNT exposure in mice increases susceptibility to respiratory viral infections [91].…”

Do Carbon Nanotubes and Asbestos Fibers Exhibit Common Toxicity Mechanisms?

“…As mentioned earlier, many studies confirmed that CNTs of various size and shape induce ROS generation, immune suppression and pulmonary fibrosis that is associated with an increased risk of lung cancer. This is mainly due to the change in the gene expression profiles related to oxidative stress response, cellular transport, metabolism and cell cycle regulation in both in vivo and in vitro systems [ 176 , 177 , 178 , 179 , 180 , 181 , 182 ].…”

“…Mukherjee and colleagues proposed that SWCNTs interact with Toll-like receptor 4 (TLR4) in the absence of a protein corona through hydrophobic interactions and attract cytokine and chemokine cascades [ 189 ]. Many recent studies focus on global mRNA and ncRNA expression profiles in the blood of workers exposed to CNTs; they have found many differentially regulated genes involved in cell cycle regulation, apoptosis and proliferation similar to those affected by asbestos fibers [ 178 , 180 , 190 ].…”