Multiwalled carbon nanotubes intratracheally instilled into the rat lung induce development of pleural malignant mesothelioma and lung tumors

Our plain-English summary of Multiwalled carbon nanotubes intratracheally instilled into the rat lung induce development of pleural malignant mesothelioma and lung tumors, by M. Suzui, M. Futakuchi, K. Fukamachi, et al (Cancer Science, 2016).

The study

• Authors: M. Suzui, M. Futakuchi, K. Fukamachi, T. Numano, M. Abdelgied, S. Takahashi, M. Ohnishi, T. Omori, S. Tsuruoka, A. Hirose, J. Kanno, Y. Sakamoto, D.B. Alexander, W.T. Alexander, X. Jiegou, H. Tsuda
• Journal: Cancer Science
• Published: 2016;107(7):924-35
• Cited by: 108 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Multiwalled carbon nanotubes (MWCNT) have a fibrous structure and physical properties similar to asbestos and have been shown to induce malignant mesothelioma of the peritoneum after injection into the scrotum or peritoneal cavity in rats and mice. For human cancer risk assessment, however, data after administration of MWCNT via the airway, the exposure route that is most relevant to humans, is required. The present study was undertaken to investigate the carcinogenicity of MWCNT-N (NIKKISO) after administration to the rat lung. MWCNT-N was fractionated by passing it through a sieve with a pore size of 25 μm. The average lengths of the MWCNT were 4.2 μm before filtration and 2.6 μm in the flow-through fraction; the length of the retained MWCNT could not be determined. For the present study, 10-week-old F344/Crj male rats were divided into five groups: no treatment, vehicle control, MWCNT-N before filtration, MWCNT-N flow-through and MWCNT-N retained groups. Administration was by the trans-tracheal intrapulmonary spraying (TIPS) method. Rats were administered a total of 1 mg/rat during the initial 2 weeks of the experiment and then observed up to 109 weeks. The incidences of malignant mesothelioma and lung tumors (bronchiolo-alveolar adenomas and carcinomas) were 6/38 and 14/38, respectively, in the three groups administered MWCNT and 0/28 and 0/28, respectively, in the control groups. All malignant mesotheliomas were localized in the pericardial pleural cavity. The sieve fractions did not have a significant effect on tumor incidence. In conclusion, administration of MWCNT to the lung in the rat induces malignant mesothelioma and lung tumors.

© 2016 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

In plain English

This rat experiment tested multiwalled carbon nanotubes (MWCNT), a manufactured fiber the authors describe as similar to asbestos. No asbestos was tested. One hundred 10-week-old male F344/Crj rats were split into five groups: no treatment, vehicle, and three MWCNT-N preparations. These were unfiltered fibers, the portion that passed through a 25 µm sieve, and the portion the sieve retained. The fibers were sprayed into the lungs through the windpipe eight times over two weeks (1 mg per rat in total). Five rats per group were killed at week 2 for lung measurements; the other 15 per group were observed to week 109. Among rats that survived at least 63 weeks, malignant mesothelioma occurred in 6 of 38 MWCNT-treated rats (15.8%) and 0 of 28 controls (P = 0.034). All were in the chest's mediastinal space. Lung tumors (adenomas and carcinomas) occurred in 14 of 38 treated rats (36.8%) and 0 of 28 controls (P < 0.001). Differences among the three preparations were not statistically significant. The authors concluded that airway exposure to MWCNT-N results in malignant mesothelioma and lung tumors in rats.

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: a 109-week carcinogenicity study in rats, with MWCNT given by trans-tracheal intrapulmonary spraying (TIPS) and tumor incidence compared with control groups using Fisher's exact test
• Who was studied: 100 male F344/Crj rats, 10 weeks old, in five groups of 20. Five rats per group were killed at week 2 to measure lung fiber content, and the remaining 15 per group were observed to week 109. Analysis included rats surviving 63 weeks or more: no treatment 15, vehicle 13, unfiltered 12, flow-through 12, retained 14.
• Exposure: MWCNT-N (NIKKISO) in three preparations: unfiltered (mean length 4.2 µm), flow-through fraction from a 25 µm sieve (mean length 2.6 µm), and retained fraction (length not measurable). Each was sprayed into the lungs at 125 µg per dose, eight times over 2 weeks, for a total of 1 mg per rat. Iron content was 0.046% by weight.
• Main results:
  • Malignant mesothelioma occurred in 6/38 (15.8%) rats in the three MWCNT groups combined, compared with 0/28 (0%) in the two control groups combined (P = 0.034).
  • Lung tumors (bronchiolo-alveolar adenoma and carcinoma) occurred in 14/38 (36.8%) MWCNT-treated rats, compared with 0/28 (0%) controls (P < 0.001).
  • Mesothelioma counts were 3 in the unfiltered group, 3 in the flow-through group and none in the retained-fraction group. The differences among the three fractions were not statistically significant.
  • There was no significant difference in lung tumor incidence or total tumor burden among the three MWCNT preparations.
  • All the malignant mesotheliomas were located in the mediastinal space of the chest. None were in the lateral parietal pleura.
  • Peritoneal (abdominal) mesotheliomas occurred in the vehicle control group (2), the flow-through group (1) and the retained group (1). They were excluded from the analysis of pleural mesotheliomas as probably arising from scrotal tissue, and tumors in other organs did not differ statistically from controls.
  • Survival times did not differ between any group and the vehicle control group.
  • At week 109, the amount of MWCNT remaining in the lungs, as a share of the amount measured at week 2, was 25.4% for unfiltered, 48.0% for flow-through and 26.3% for the retained fraction.
• The authors' conclusion: The authors concluded that exposure of rats to 1 mg MWCNT-N per rat via the airway results in malignant mesothelioma and lung alveolar cell tumors.
• Limitations the authors state:
  • The primary site of the mesotheliomas could not be determined because the tumors were at an advanced stage.
  • The fiber length in the retained fraction could not be measured because the fibers formed dense clumps.
  • The route by which MWCNT moved from the lung to the pleura was not established.

Topics

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

Medical terms in this study, explained in our Lexicon: Malignant Mesothelioma, Peritoneum, Peritoneal Cavity, Carcinoma, Pericardial, Pleural Cavity.

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• Size- and shape-dependent pleural translocation, deposition, fibrogenesis, and mesothelial proliferation by multiwalled carbon nanotubes — J. Xu, D.B. Alexander, et al. (2014)
• Persistent Pleural Lesions and Inflammation by Pulmonary Exposure of Multiwalled Carbon Nanotubes — D. Liao, Q. Wang, et al. (2018)
• 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)
• MWCNT-7 administered to the lung by intratracheal instillation induces development of pleural mesothelioma in F344 rats — T. Numano, H. Higuchi, et al. (2019)
• Comparative proteomics and pulmonary toxicity of instilled single-walled carbon nanotubes, crocidolite asbestos, and ultrafine carbon black in mice — J.G. Teeguarden, B.J. Webb-Robertson, et al. (2011)

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