Abstract We previously investigated the carcinogenic potential of different types of carbon nanotubes (CNTs) in rats. Rigid and straight CNTs (MWCNT-7 and MWCNT-N) caused lung cancer and pleural mesothelioma. Thin and tangled CNTs (MWCNT-B, DWCNT and SWCNT) induced lung cancer. Exposure to carbon nano horns (CNHs) and carbon nano brushes (CNBs) did not cause lung or pleural tumours. To obtain molecular insights into CNT-induced lung carcinogenicity, we performed a transcriptomic analysis of lung tissues of male F344 rats exposed to four doses of carcinogenic CNTs (MWCNT-7, MWCNT-N, MWCNT-B, DWCNT, SWCNT) or non-carcinogenic CNH injected by TIPS at total dose of 0.5 mg/rat and compared it with those induced by DHPN (a known chemical carcinogen) injected intraperitoneally at total dose of 1,000 mg/rat. Pulmonary toxicity and the entire gene expression profiles were analysed six weeks after the final dose. The RNA- sequencing analysis identified a large number of significantly differentially expressed genes between groups. The GO enrichment analysis revealed that the genes of phagocytes regulating migration and chemotaxis up-regulated in carcinogenic CNTs versus non-carcinogenic CNH. The KEGG analysis revealed that exposure to carcinogenic CNTs up-regulated inflammation-elicited signalling pathways: cytokine signalling pathways, cytokine-cytokine receptor interaction, IL-17 signalling pathway and TNF signalling pathway. Interestingly, the gene expression profile of carcinogenic CNT was totally different compared to that of DPHN-treated rats. qRT-PCR indicated that expression of inflammatory cytokines, Ccl2, Ccl3, Ccl9, Il-1b and TGF-b up-regulated by carcinogenic CNTs but not by DHPN. Our findings support a scenario of inflammation-induced carcinogenesis and contribute to a better understanding of the molecular mechanism of CNT carcinogenicity.
Ahmed et al. (Thu,) studied this question.