{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T15:46:25Z","timestamp":1785599185932,"version":"3.56.0"},"reference-count":60,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2025,11,29]],"date-time":"2025-11-29T00:00:00Z","timestamp":1764374400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Health and Labour Sciences Research Grants from the Ministry of Health, Labour and Welfare of Japan","award":["19KD1001"],"award-info":[{"award-number":["19KD1001"]}]},{"name":"Health and Labour Sciences Research Grants from the Ministry of Health, Labour and Welfare of Japan","award":["25KD2003"],"award-info":[{"award-number":["25KD2003"]}]},{"name":"Nishimura International Scholarship Foundation, Japan"},{"name":"Ichikawa International Scholarship Foundation, Japan"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nanomaterials"],"abstract":"<jats:p>Although numerous experimental studies have demonstrated the carcinogenic potential of multi-walled carbon nanotubes (MWCNTs) in lungs, the underlying molecular mechanisms\u2014especially gene expression changes associated with different tumor types\u2014remain poorly characterized. To elucidate the molecular signatures associated with MWCNT-induced carcinogenesis, we performed microarray-based gene expression profiling of rat lung tumors induced by MWCNT-7, including both adenocarcinoma (ADC) and malignant mesothelioma (MM), as well as ADCs induced by two types of double-walled CNTs (DWCNTs) differing in fiber length (1.5 \u00b5m and 7 \u00b5m). Hierarchical clustering revealed that the MWCNT-7-induced MM exhibited a gene expression profile distinct from the ADCs. The ADCs induced by the DWCNTs and the ADC induced by MWCNT-7 shared several pathways that were distinct from those of the MWCNT-7 induced MM. The distinct pathways upregulated in the ADCs versus the MM support the conclusion that MWCNT-induced ADCs arise through distinct biological mechanisms compared to MWCNT-induced MMs and identified tumor-type-specific biomarker candidates: complement factor I (CFI) and secreted phosphoprotein 1 (SPP1) for ADCs, and fibronectin 1 (FN1) for MM. In addition, the gene expression profiles of the ADCs induced by the three fiber types indicate that both types of thin flexible DWCNTs used in the present study promoted a number of carcinogenic pathways in the rat lung that were also promoted by MWCNT-7, which is a class 2B carcinogen. These results support the conclusion that DWCNTs are carcinogenic in the rat lung and highlight the importance of further assessments of the potential lung carcinogenicity of inhaled thin flexible CNTs.<\/jats:p>","DOI":"10.3390\/nano15231806","type":"journal-article","created":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T08:49:22Z","timestamp":1764665362000},"page":"1806","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Comparative Gene Expression Analysis of Malignant Mesothelioma and Lung Adenocarcinomas Induced by Multi-Walled Carbon Nanotube-7 and Double-Walled Carbon Nanotubes in Rats: Distinct Molecular Signatures and Canonical Pathways"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1642-8127","authenticated-orcid":false,"given":"Min","family":"Gi","sequence":"first","affiliation":[{"name":"Department of Environmental Risk Assessment, Graduate School of Medicine, Osaka Metropolitan University, Osaka 545-8585, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8938-9670","authenticated-orcid":false,"given":"Shugo","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Department of Molecular Pathology, Graduate School of Medicine, Osaka Metropolitan University, Osaka 545-8585, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8848-6708","authenticated-orcid":false,"given":"Dina Mourad","family":"Saleh","sequence":"additional","affiliation":[{"name":"Nanotoxicology Project, Nagoya City University Graduate School of Medical Sciences, Nagoya 467-8603, Japan"},{"name":"Department of Forensic Medicine and Clinical Toxicology, Faculty of Medicine, Assiut University, Assiut 71515, Egypt"},{"name":"Center of Excellence for Toxicological Testing, Mammalian and Aquatic Toxicology Department, Central Agricultural Pesticides Lab, Agricultural Research Center, Dokki, Giza 12618, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5241-2195","authenticated-orcid":false,"given":"Omnia Hosny Mohamed","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Nanotoxicology Project, Nagoya City University Graduate School of Medical Sciences, Nagoya 467-8603, Japan"},{"name":"Department of Forensic Medicine and Clinical Toxicology, Faculty of Medicine, Aswan University, Aswan 81528, Egypt"},{"name":"Department of Experimental Pathology and Tumor Biology, Graduate School of Medical Sciences, Nagoya City University, Nagoya 467-8601, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William T.","family":"Alexander","sequence":"additional","affiliation":[{"name":"Nanotoxicology Project, Nagoya City University Graduate School of Medical Sciences, Nagoya 467-8603, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masaki","family":"Fujioka","sequence":"additional","affiliation":[{"name":"Department of Molecular Pathology, Graduate School of Medicine, Osaka Metropolitan University, Osaka 545-8585, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arpamas","family":"Vachiraarunwong","sequence":"additional","affiliation":[{"name":"Department of Environmental Risk Assessment, Graduate School of Medicine, Osaka Metropolitan University, Osaka 545-8585, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Runjie","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Environmental Risk Assessment, Graduate School of Medicine, Osaka Metropolitan University, Osaka 545-8585, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guiyu","family":"Qiu","sequence":"additional","affiliation":[{"name":"Department of Environmental Risk Assessment, Graduate School of Medicine, Osaka Metropolitan University, Osaka 545-8585, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ikue","family":"Noura","sequence":"additional","affiliation":[{"name":"Department of Molecular Pathology, Graduate School of Medicine, Osaka Metropolitan University, Osaka 545-8585, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1149-1450","authenticated-orcid":false,"given":"Anna","family":"Kakehashi","sequence":"additional","affiliation":[{"name":"Department of Molecular Pathology, Graduate School of Medicine, Osaka Metropolitan University, Osaka 545-8585, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-Li","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Toxicology, School of Public Health, Southern Medical University, Guangzhou 510515, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuji","family":"Tsuruoka","sequence":"additional","affiliation":[{"name":"Neura Inc., Tokyo 100-0005, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1703-4883","authenticated-orcid":false,"given":"Akihiko","family":"Hirose","sequence":"additional","affiliation":[{"name":"Chemicals Assessment and Research Center, Chemicals Evaluation and Research Institute, Tokyo 112-0004, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0828-2033","authenticated-orcid":false,"given":"Aya","family":"Naiki-Ito","sequence":"additional","affiliation":[{"name":"Department of Experimental Pathology and Tumor Biology, Graduate School of Medical Sciences, Nagoya City University, Nagoya 467-8601, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroyuki","family":"Tsuda","sequence":"additional","affiliation":[{"name":"Nanotoxicology Project, Nagoya City University Graduate School of Medical Sciences, Nagoya 467-8603, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideki","family":"Wanibuchi","sequence":"additional","affiliation":[{"name":"Department of Environmental Risk Assessment, Graduate School of Medicine, Osaka Metropolitan University, Osaka 545-8585, Japan"},{"name":"Department of Molecular Pathology, Graduate School of Medicine, Osaka Metropolitan University, Osaka 545-8585, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1126\/science.1222453","article-title":"Carbon nanotubes: Present and future commercial 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