MWCNT-7 administered to the lung by intratracheal instillation induces development of pleural mesothelioma in F344 rats

Our plain-English summary of MWCNT-7 administered to the lung by intratracheal instillation induces development of pleural mesothelioma in F344 rats, by T. Numano, H. Higuchi, D.B. Alexander, et al (Cancer Science, 2019).

The study

• Authors: T. Numano, H. Higuchi, D.B. Alexander, W.T. Alexander, M. Abdelgied, A.M. El-Gazzar, D. Saleh, H. Takase, A. Hirose, A. Naiki-Ito, S. Suzuki, S. Takahashi, H. Tsuda
• Journal: Cancer Science
• Published: 2019;110(8):2485-2492
• Cited by: 43 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Multi-walled carbon nanotube-7 (MWCNT-7) fibers are biopersistent and have a structure similar to asbestos. MWCNT-7 has been shown to induce malignant mesothelioma when administered by intrascrotal or intraperitoneal injection in rats and mice, and an inhalation study demonstrated that rats exposed to respirable MWCNT-7 developed lung tumors. MWCNT-N, which is similar to MWCNT-7, was shown to induce both lung tumors and malignant mesothelioma in rats when administered by trans-tracheal intrapulmonary spraying (TIPS). The present study was performed to investigate the carcinogenicity of MWCNT-7 when administered by the TIPS method. Ten-week-old male F344/Crj rats were divided into 3 groups and administered 0.5 mL vehicle, 0.250 μg/mL MWCNT-7 or 0.250 μg/mL crocidolite once a week for 12 weeks (total doses of 1.5 mg/rat) and then observed for up to 104 weeks. Rats in the MWCNT-7 group began to die from pathologies associated with the development of malignant mesothelioma 35 weeks after the final TIPS administration. Overall, the incidence of malignant mesothelioma in the MWCNT-7 group was significantly higher than in the vehicle or crocidolite groups.

© 2019 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

In plain English

In this animal experiment, the authors tested whether a multi-walled carbon nanotube called MWCNT-7 causes cancer when sprayed into rats' lungs. Male F344 rats were sprayed through the windpipe once a week for 12 weeks with carrier liquid alone, MWCNT-7, or crocidolite asbestos; each MWCNT-7 or crocidolite rat received 1.5 mg in total. They were observed until study week 104. Malignant mesothelioma developed in 18 of 19 rats given MWCNT-7, and in none of the rats in the carrier-liquid group (15 rats) or the crocidolite group (19 rats). The first death linked to mesothelioma came at week 47. At week 104, 5% of MWCNT-7 rats were alive, compared with 79% of crocidolite rats and 80% of carrier-liquid rats. Lung tumors (adenomas and adenocarcinomas combined) occurred in 1 of 15 carrier-liquid, 5 of 19 crocidolite and 1 of 19 MWCNT-7 rats, with no significant differences. The authors concluded that MWCNT-7 given through the airway resulted in malignant pleural mesothelioma in rats. Because all the tumors were late-stage, they could not tell where they began.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Animal experiment (carcinogenicity study in rats) with three randomly assigned groups: vehicle control, MWCNT-7 and crocidolite
• Who was studied: Male F344/DuCrlCrj rats from Charles River Laboratories Japan, nine weeks old on arrival. Rats examined: 15 in the vehicle group, 19 in the MWCNT-7 group and 19 in the crocidolite group. One rat each in the MWCNT-7 and crocidolite groups died during instillation and was excluded. Rats were observed until study week 104, with weeks counted from the start of the study.
• Exposure: Each rat received 0.5 mL of vehicle (saline with 0.5% Pluronic F68), MWCNT-7 suspension (250 μg/mL) or crocidolite suspension (250 μg/mL). The liquid was sprayed into the lungs through the trachea by intra-tracheal intrapulmonary spraying (TIPS) once a week for 12 weeks. Each rat in the MWCNT-7 and crocidolite groups received a total test-material dose of 1.5 mg.
• Main results:
  • Malignant mesothelioma developed in 18 of 19 rats in the MWCNT-7 group (95%, significantly different from the vehicle group at P less than 0.001).
  • No rats in the vehicle control group or the crocidolite group developed malignant mesothelioma.
  • The first rat to die from pathologies associated with malignant mesothelioma died at week 47.
  • Survival at week 104 was 5% in the MWCNT-7 group, 79% in the crocidolite group and 80% in the vehicle group.
  • Average survival was 78.6 weeks in the MWCNT-7 group, 102.4 weeks in the crocidolite group and 101.5 weeks in the vehicle group. The decrease was significant for MWCNT-7 compared with vehicle, but not for crocidolite compared with vehicle.
  • Combined incidence of lung adenomas and adenocarcinomas was 1/15 in the vehicle group, 5/19 in the crocidolite group and 1/19 in the MWCNT-7 group. There was no significant difference between either treated group and the vehicle group.
  • Epithelial type II cell hyperplasia in the lung was significantly more common in the crocidolite group (8/19) and the MWCNT-7 group (17/19) than in the vehicle group (1/15).
  • MWCNT-7 fibers measured in the lung had a mean length of 4.8 plus or minus 2.8 μm (median 4.2 μm). Fibers in the mediastinal lymph node had a mean length of 3.0 plus or minus 1.6 μm (median 2.7 μm), which was significantly shorter. 300 fibers were examined in each tissue.
  • MWCNT-7 fibers were found in the mesotheliomas of the MWCNT-7-treated rats, mainly associated with macrophages.
  • Body weight in the MWCNT-7 group was slightly but significantly lower than in controls from week 6 to week 80 and at weeks 88 and 96.
• The authors' conclusion: The authors concluded that giving MWCNT-7 through the airway by TIPS resulted in malignant pleural mesothelioma in rats.
• Limitations the authors state:
  • All the mesotheliomas were late-stage, so the site where they first developed could not be determined.
  • The authors suggested that the MWCNT-7 rats most likely did not develop lung adenocarcinomas because they died early from mesothelioma-related disease, which limited the assessment of lung tumors in that group.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Crocidolite, Lung cancer, Mesothelioma.

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Malignant Mesothelioma, Crocidolite.

Related studies

• Comparative carcinogenicity study of a thick, straight-type and a thin, tangled-type multi-walled carbon nanotube administered by intra-tracheal instillation in the rat — D.M. Saleh, W.T. Alexander, et al. (2020)
• Pulmonary and pleural toxicity of potassium octatitanate fibers, rutile titanium dioxide nanoparticles, and MWCNT-7 in male Fischer 344 rats — M. Abdelgied, A.M. El-Gazzar, et al. (2019)
• Multiwalled carbon nanotubes intratracheally instilled into the rat lung induce development of pleural malignant mesothelioma and lung tumors — M. Suzui, M. Futakuchi, et al. (2016)
• Potassium octatitanate fibers induce persistent lung and pleural injury and are possibly carcinogenic in male Fischer 344 rats — M. Abdelgied, A.M. El-Gazzar, et al. (2018)
• Multi-walled carbon nanotubes translocate into the pleural cavity and induce visceral mesothelial proliferation in rats — J. Xu, M. Futakuchi, et al. (2012)
• Carcinogenic effect of potassium octatitanate (POT) fibers in the lung and pleura of male Fischer 344 rats after intrapulmonary administration — M. Abdelgied, A.M. El-Gazzar, et al. (2019)

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