In Vivo Genotoxicity Assessment of a Multiwalled Carbon Nanotube in a Mouse Ex Vivo Culture

Overview

Journal Genes Environ

Publisher Biomed Central

Specialty Environmental Health

Date 2022 Oct 18

PMID 36258253

Authors

Katsuyoshi Horibata

Hironao Takasawa

Motoki Hojo

Yuhji Taquahashi

Miyuki Shigano

Satoshi Yokota

Norihiro Kobayashi

Kei-Ichi Sugiyama

Masamitsu Honma

Shuichi Hamada

Affiliations

Soon will be listed here.

Abstract

Background: Multiwalled carbon nanotubes (MWCNTs) are suspected lung carcinogens because their shape and size are similar to asbestos. Various MWCNT types are manufactured; however, only MWNT-7 is classified into Group 2B by The International Agency for Research on Cancer. MWNT-7's carcinogenicity is strongly related to inflammatory reactions. On the other hand, inconsistent results on MWNT-7 genotoxicity have been reported. We previously observed no significant differences in both Pig-a (blood) and gpt (lung) mutant frequencies between MWNT-7-intratracheally treated and negative control rats. In this study, to investigate in vivo MWNT-7 genotoxicity on various endpoints, we attempted to develop a lung micronucleus assay through ex vivo culture targeting the cellular fraction of Clara cells and alveolar Type II (AT-II) cells, known as the initiating cells of lung cancer. Using this system, we analyzed the in vivo MWNT-7 genotoxicity induced by both whole-body inhalation exposure and intratracheal instillation. We also conducted an erythrocyte micronucleus assay using the samples obtained from animals under intratracheal instillation to investigate the tissue specificity of MWNT-7 induced genotoxicities.

Results: We detected a significant increase in the incidence of micronucleated cells derived from the cellular fraction of Clara cells and AT-II cells in both MWNT-7-treated and positive control groups compared to the negative control group under both whole-body inhalation exposures and intratracheal instillation. Additionally, the erythrocyte micronucleus assay detected a significant increase in the incidence of micronucleated reticulocytes only in the positive control group.

Conclusions: Our findings indicated that MWNT-7 was genotoxic in the lungs directly exposed by both the body inhalation and intratracheal instillation but not in the hematopoietic tissue.

Citing Articles

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

Hojo M, Maeno A, Sakamoto Y, Yamamoto Y, Taquahashi Y, Hirose A Nanomaterials (Basel). 2023; 13(14).

PMID: 37513116 PMC: 10383707. DOI: 10.3390/nano13142105.

Current status and future challenges of genotoxicity OECD Test Guidelines for nanomaterials: a workshop report.

Doak S, Andreoli C, Burgum M, Chaudhry Q, Bleeker E, Bossa C Mutagenesis. 2023; 38(4):183-191.

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