Two-year intermittent exposure of a multiwalled carbon nanotube by intratracheal instillation induces lung tumors and pleural mesotheliomas in F344 rats
Abstract Background A mounting number of studies have been documenting the carcinogenic potential of multiwalled carbon nanotubes (MWCNTs); however, only a few studies have evaluated the pulmonary carcinogenicity of MWCNTs in vivo. A 2-year inhalation study demonstrated that MWNT-7, a widely used MW...
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| Format: | Article |
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BMC
2022-05-01
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| Series: | Particle and Fibre Toxicology |
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| Online Access: | https://doi.org/10.1186/s12989-022-00478-7 |
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| author | Motoki Hojo Ai Maeno Yoshimitsu Sakamoto Aya Ohnuki Yukie Tada Yukio Yamamoto Kiyomi Ikushima Ryota Inaba Jin Suzuki Yuhji Taquahashi Satoshi Yokota Norihiro Kobayashi Makoto Ohnishi Yuko Goto Takamasa Numano Hiroyuki Tsuda David B. Alexander Jun Kanno Akihiko Hirose Akiko Inomata Dai Nakae |
| author_facet | Motoki Hojo Ai Maeno Yoshimitsu Sakamoto Aya Ohnuki Yukie Tada Yukio Yamamoto Kiyomi Ikushima Ryota Inaba Jin Suzuki Yuhji Taquahashi Satoshi Yokota Norihiro Kobayashi Makoto Ohnishi Yuko Goto Takamasa Numano Hiroyuki Tsuda David B. Alexander Jun Kanno Akihiko Hirose Akiko Inomata Dai Nakae |
| author_sort | Motoki Hojo |
| collection | DOAJ |
| description | Abstract Background A mounting number of studies have been documenting the carcinogenic potential of multiwalled carbon nanotubes (MWCNTs); however, only a few studies have evaluated the pulmonary carcinogenicity of MWCNTs in vivo. A 2-year inhalation study demonstrated that MWNT-7, a widely used MWCNT, was a pulmonary carcinogen in rats. In another 2-year study, rats administered MWNT-7 by intratracheal instillation at the beginning of the experimental period developed pleural mesotheliomas but not lung tumors. To obtain data more comparable with rats exposed to MWNT-7 by inhalation, we administered MWNT-7 to F344 rats by intratracheal instillation once every 4-weeks over the course of 2 years at 0, 0.125, and 0.5 mg/kg body weight, allowing lung burdens of MWNT-7 to increase over the entire experimental period, similar to the inhalation study. Results Absolute and relative lung weights were significantly elevated in both MWNT-7-treated groups. Dose- and time-dependent toxic effects in the lung and pleura, such as inflammatory, fibrotic, and hyperplastic lesions, were found in both treated groups. The incidences of lung carcinomas, lung adenomas, and pleural mesotheliomas were significantly increased in the high-dose group compared with the control group. The pleural mesotheliomas developed mainly at the mediastinum. No MWNT-7-related neoplastic lesions were noted in the other organs. Cytological and biochemical parameters of the bronchoalveolar lavage fluid (BALF) were elevated in both treated groups. The lung burden of MWNT-7 was dose- and time-dependent, and at the terminal necropsy, the average value was 0.9 and 3.6 mg/lung in the low-dose and high-dose groups, respectively. The number of fibers in the pleural cavity was also dose- and time-dependent. Conclusions Repeated administration of MWNT-7 by intratracheal instillation over the 2 years indicates that MWNT-7 is carcinogenic to both the lung and pleura of rats, which differs from the results of the 2 carcinogenicity tests by inhalation or intratracheal instillation. |
| first_indexed | 2024-04-12T16:12:25Z |
| format | Article |
| id | doaj.art-206a844169344007b85b1a278d8bca76 |
| institution | Directory Open Access Journal |
| issn | 1743-8977 |
| language | English |
| last_indexed | 2024-04-12T16:12:25Z |
| publishDate | 2022-05-01 |
| publisher | BMC |
| record_format | Article |
| series | Particle and Fibre Toxicology |
| spelling | doaj.art-206a844169344007b85b1a278d8bca762022-12-22T03:25:51ZengBMCParticle and Fibre Toxicology1743-89772022-05-0119112310.1186/s12989-022-00478-7Two-year intermittent exposure of a multiwalled carbon nanotube by intratracheal instillation induces lung tumors and pleural mesotheliomas in F344 ratsMotoki Hojo0Ai Maeno1Yoshimitsu Sakamoto2Aya Ohnuki3Yukie Tada4Yukio Yamamoto5Kiyomi Ikushima6Ryota Inaba7Jin Suzuki8Yuhji Taquahashi9Satoshi Yokota10Norihiro Kobayashi11Makoto Ohnishi12Yuko Goto13Takamasa Numano14Hiroyuki Tsuda15David B. Alexander16Jun Kanno17Akihiko Hirose18Akiko Inomata19Dai Nakae20Department of Pharmaceutical and Environmental Sciences, Tokyo Metropolitan Institute of Public HealthDepartment of Pharmaceutical and Environmental Sciences, Tokyo Metropolitan Institute of Public HealthDepartment of Pharmaceutical and Environmental Sciences, Tokyo Metropolitan Institute of Public HealthDepartment of Pharmaceutical and Environmental Sciences, Tokyo Metropolitan Institute of Public HealthDepartment of Pharmaceutical and Environmental Sciences, Tokyo Metropolitan Institute of Public HealthDepartment of Pharmaceutical and Environmental Sciences, Tokyo Metropolitan Institute of Public HealthDepartment of Pharmaceutical and Environmental Sciences, Tokyo Metropolitan Institute of Public HealthDepartment of Pharmaceutical and Environmental Sciences, Tokyo Metropolitan Institute of Public HealthDepartment of Pharmaceutical and Environmental Sciences, Tokyo Metropolitan Institute of Public HealthCenter for Biological Safety and Research, National Institute of Health SciencesCenter for Biological Safety and Research, National Institute of Health SciencesCenter for Biological Safety and Research, National Institute of Health SciencesJapan Bioassay Research Center, Japan Organization of Occupational Health and SafetyJapan Bioassay Research Center, Japan Organization of Occupational Health and SafetyDIMS Institute of Medical ScienceNanotoxicology Project, Nagoya City UniversityNanotoxicology Project, Nagoya City UniversityCenter for Biological Safety and Research, National Institute of Health SciencesCenter for Biological Safety and Research, National Institute of Health SciencesDepartment of Pharmaceutical and Environmental Sciences, Tokyo Metropolitan Institute of Public HealthAnimal Medical Course, Department of Medical Sports, Faculty of Health Care and Medical Sports, Teikyo Heisei UniversityAbstract Background A mounting number of studies have been documenting the carcinogenic potential of multiwalled carbon nanotubes (MWCNTs); however, only a few studies have evaluated the pulmonary carcinogenicity of MWCNTs in vivo. A 2-year inhalation study demonstrated that MWNT-7, a widely used MWCNT, was a pulmonary carcinogen in rats. In another 2-year study, rats administered MWNT-7 by intratracheal instillation at the beginning of the experimental period developed pleural mesotheliomas but not lung tumors. To obtain data more comparable with rats exposed to MWNT-7 by inhalation, we administered MWNT-7 to F344 rats by intratracheal instillation once every 4-weeks over the course of 2 years at 0, 0.125, and 0.5 mg/kg body weight, allowing lung burdens of MWNT-7 to increase over the entire experimental period, similar to the inhalation study. Results Absolute and relative lung weights were significantly elevated in both MWNT-7-treated groups. Dose- and time-dependent toxic effects in the lung and pleura, such as inflammatory, fibrotic, and hyperplastic lesions, were found in both treated groups. The incidences of lung carcinomas, lung adenomas, and pleural mesotheliomas were significantly increased in the high-dose group compared with the control group. The pleural mesotheliomas developed mainly at the mediastinum. No MWNT-7-related neoplastic lesions were noted in the other organs. Cytological and biochemical parameters of the bronchoalveolar lavage fluid (BALF) were elevated in both treated groups. The lung burden of MWNT-7 was dose- and time-dependent, and at the terminal necropsy, the average value was 0.9 and 3.6 mg/lung in the low-dose and high-dose groups, respectively. The number of fibers in the pleural cavity was also dose- and time-dependent. Conclusions Repeated administration of MWNT-7 by intratracheal instillation over the 2 years indicates that MWNT-7 is carcinogenic to both the lung and pleura of rats, which differs from the results of the 2 carcinogenicity tests by inhalation or intratracheal instillation.https://doi.org/10.1186/s12989-022-00478-7MWCNTCarcinogenicityIntratracheal instillationLung tumorsPleural mesotheliomaLung burden |
| spellingShingle | Motoki Hojo Ai Maeno Yoshimitsu Sakamoto Aya Ohnuki Yukie Tada Yukio Yamamoto Kiyomi Ikushima Ryota Inaba Jin Suzuki Yuhji Taquahashi Satoshi Yokota Norihiro Kobayashi Makoto Ohnishi Yuko Goto Takamasa Numano Hiroyuki Tsuda David B. Alexander Jun Kanno Akihiko Hirose Akiko Inomata Dai Nakae Two-year intermittent exposure of a multiwalled carbon nanotube by intratracheal instillation induces lung tumors and pleural mesotheliomas in F344 rats Particle and Fibre Toxicology MWCNT Carcinogenicity Intratracheal instillation Lung tumors Pleural mesothelioma Lung burden |
| title | Two-year intermittent exposure of a multiwalled carbon nanotube by intratracheal instillation induces lung tumors and pleural mesotheliomas in F344 rats |
| title_full | Two-year intermittent exposure of a multiwalled carbon nanotube by intratracheal instillation induces lung tumors and pleural mesotheliomas in F344 rats |
| title_fullStr | Two-year intermittent exposure of a multiwalled carbon nanotube by intratracheal instillation induces lung tumors and pleural mesotheliomas in F344 rats |
| title_full_unstemmed | Two-year intermittent exposure of a multiwalled carbon nanotube by intratracheal instillation induces lung tumors and pleural mesotheliomas in F344 rats |
| title_short | Two-year intermittent exposure of a multiwalled carbon nanotube by intratracheal instillation induces lung tumors and pleural mesotheliomas in F344 rats |
| title_sort | two year intermittent exposure of a multiwalled carbon nanotube by intratracheal instillation induces lung tumors and pleural mesotheliomas in f344 rats |
| topic | MWCNT Carcinogenicity Intratracheal instillation Lung tumors Pleural mesothelioma Lung burden |
| url | https://doi.org/10.1186/s12989-022-00478-7 |
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