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Article

Time-Course of Transcriptomic Change in the Lungs of F344 Rats Repeatedly Exposed to a Multiwalled Carbon Nanotube in a 2-Year Test

by
Motoki Hojo
1,*,
Ai Maeno
1,
Yoshimitsu Sakamoto
1,
Yukio Yamamoto
1,
Yuhji Taquahashi
2,
Akihiko Hirose
3,
Jin Suzuki
1,
Akiko Inomata
1 and
Dai Nakae
4,*
1
Department of Pharmaceutical and Environmental Sciences, Tokyo Metropolitan Institute of Public Health, 3-24-1 Hyakunincho, Shinjuku-ku, Tokyo 169-0073, Japan
2
Division of Cellular and Molecular Toxicology, Center for Biological Safety and Research, National Institute of Health Sciences, 3-25-26 Tono-machi, Kawasaki-ku, Kawasaki 210-9501, Kanagawa, Japan
3
Chemicals Assessment and Research Center, Chemicals Evaluation and Research Institute, Japan, 1-4-25 Koraku, Bunkyo-ku, Tokyo 112-0004, Japan
4
Department of Medical Sports, Faculty of Health Care and Medical Sports, Teikyo Heisei University, 4-1 Uruido-Minami, Ichihara 290-0193, Chiba, Japan
*
Authors to whom correspondence should be addressed.
Nanomaterials 2023, 13(14), 2105; https://doi.org/10.3390/nano13142105
Submission received: 9 June 2023 / Revised: 13 July 2023 / Accepted: 17 July 2023 / Published: 19 July 2023
(This article belongs to the Special Issue Safety and Toxicity of Carbon Nanotubes, Nanoparticles and Other Nanomaterials)
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Abstract

Despite intensive toxicological studies of carbon nanotubes (CNTs) over the last two decades, only a few studies have demonstrated their pulmonary carcinogenicities in chronic animal experiments, and the underlying molecular mechanisms are still unclear. To obtain molecular insights into CNT-induced lung carcinogenicity, we performed a transcriptomic analysis using a set of lung tissues collected from rats in a 2-year study, in which lung tumors were induced by repeated intratracheal instillations of a multiwalled carbon nanotube, MWNT-7. The RNA-seq-based transcriptome identified a large number of significantly differentially expressed genes at Year 0.5, Year 1, and Year 2. Ingenuity Pathway Analysis revealed that macrophage-elicited signaling pathways such as phagocytosis, acute phase response, and Toll-like receptor signaling were activated throughout the experimental period. At Year 2, cancer-related pathways including ERBB signaling and some axonal guidance signaling pathways such as EphB4 signaling were perturbed. qRT-PCR and immunohistochemistry indicated that several key molecules such as Osteopontin/Spp1, Hmox1, Mmp12, and ERBB2 were markedly altered and/or localized in the preneoplastic lesions, suggesting their participation in the induction of lung cancer. Our findings support a scenario of inflammation-induced carcinogenesis and contribute to a better understanding of the molecular mechanism of MWCNT carcinogenicity.
Keywords: carbon nanotubes; lung cancer; transcriptomics; inflammation; intratracheal instillation; MWNT-7; F344 rats carbon nanotubes; lung cancer; transcriptomics; inflammation; intratracheal instillation; MWNT-7; F344 rats

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MDPI and ACS Style

Hojo, M.; Maeno, A.; Sakamoto, Y.; Yamamoto, Y.; Taquahashi, Y.; Hirose, A.; Suzuki, J.; Inomata, A.; Nakae, D. Time-Course of Transcriptomic Change in the Lungs of F344 Rats Repeatedly Exposed to a Multiwalled Carbon Nanotube in a 2-Year Test. Nanomaterials 2023, 13, 2105. https://doi.org/10.3390/nano13142105

AMA Style

Hojo M, Maeno A, Sakamoto Y, Yamamoto Y, Taquahashi Y, Hirose A, Suzuki J, Inomata A, Nakae D. Time-Course of Transcriptomic Change in the Lungs of F344 Rats Repeatedly Exposed to a Multiwalled Carbon Nanotube in a 2-Year Test. Nanomaterials. 2023; 13(14):2105. https://doi.org/10.3390/nano13142105

Chicago/Turabian Style

Hojo, Motoki, Ai Maeno, Yoshimitsu Sakamoto, Yukio Yamamoto, Yuhji Taquahashi, Akihiko Hirose, Jin Suzuki, Akiko Inomata, and Dai Nakae. 2023. "Time-Course of Transcriptomic Change in the Lungs of F344 Rats Repeatedly Exposed to a Multiwalled Carbon Nanotube in a 2-Year Test" Nanomaterials 13, no. 14: 2105. https://doi.org/10.3390/nano13142105

APA Style

Hojo, M., Maeno, A., Sakamoto, Y., Yamamoto, Y., Taquahashi, Y., Hirose, A., Suzuki, J., Inomata, A., & Nakae, D. (2023). Time-Course of Transcriptomic Change in the Lungs of F344 Rats Repeatedly Exposed to a Multiwalled Carbon Nanotube in a 2-Year Test. Nanomaterials, 13(14), 2105. https://doi.org/10.3390/nano13142105

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