Cargando…

Magnetite Nanoparticles Induce Genotoxicity in the Lungs of Mice via Inflammatory Response

Nanomaterials are useful for their characteristic properties and are commonly used in various fields. Nanosized-magnetite (MGT) is widely utilized in medicinal and industrial fields, whereas their toxicological properties are not well documented. A safety assessment is thus urgently required for MGT...

Descripción completa

Detalles Bibliográficos
Autores principales: Totsuka, Yukari, Ishino, Kousuke, Kato, Tatsuya, Goto, Sumio, Tada, Yukie, Nakae, Dai, Watanabe, Masatoshi, Wakabayashi, Keiji
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5304606/
https://www.ncbi.nlm.nih.gov/pubmed/28348291
http://dx.doi.org/10.3390/nano4010175
_version_ 1782506911964332032
author Totsuka, Yukari
Ishino, Kousuke
Kato, Tatsuya
Goto, Sumio
Tada, Yukie
Nakae, Dai
Watanabe, Masatoshi
Wakabayashi, Keiji
author_facet Totsuka, Yukari
Ishino, Kousuke
Kato, Tatsuya
Goto, Sumio
Tada, Yukie
Nakae, Dai
Watanabe, Masatoshi
Wakabayashi, Keiji
author_sort Totsuka, Yukari
collection PubMed
description Nanomaterials are useful for their characteristic properties and are commonly used in various fields. Nanosized-magnetite (MGT) is widely utilized in medicinal and industrial fields, whereas their toxicological properties are not well documented. A safety assessment is thus urgently required for MGT, and genotoxicity is one of the most serious concerns. In the present study, we examined genotoxic effects of MGT using mice and revealed that DNA damage analyzed by a comet assay in the lungs of imprinting control region (ICR) mice intratracheally instilled with a single dose of 0.05 or 0.2 mg/animal of MGT was approximately two- to three-fold higher than that of vehicle-control animals. Furthermore, in gpt delta transgenic mice, gpt mutant frequency (MF) in the lungs of the group exposed to four consecutive doses of 0.2 mg MGT was significantly higher than in the control group. Mutation spectrum analysis showed that base substitutions were predominantly induced by MGT, among which G:C to A:T transition and G:C to T:A transversion were the most significant. To clarify the mechanism of mutation caused by MGT, we analyzed the formation of DNA adducts in the lungs of mice exposed to MGT. DNA was extracted from lungs of mice 3, 24, 72 and 168 h after intratracheal instillation of 0.2 mg/body of MGT, and digested enzymatically. 8-Oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG) and lipid peroxide-related DNA adducts were quantified by stable isotope dilution liquid chromatography-mass spectrometry (LC-MS/MS). Compared with vehicle control, these DNA adduct levels were significantly increased in the MGT-treated mice. In addition to oxidative stress- and inflammation related-DNA adduct formations, inflammatory cell infiltration and focal granulomatous formations were also observed in the lungs of MGT-treated mice. Based on these findings, it is suggested that inflammatory responses are probably involved in the genotoxicity induced by MGT in the lungs of mice.
format Online
Article
Text
id pubmed-5304606
institution National Center for Biotechnology Information
language English
publishDate 2014
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-53046062017-03-21 Magnetite Nanoparticles Induce Genotoxicity in the Lungs of Mice via Inflammatory Response Totsuka, Yukari Ishino, Kousuke Kato, Tatsuya Goto, Sumio Tada, Yukie Nakae, Dai Watanabe, Masatoshi Wakabayashi, Keiji Nanomaterials (Basel) Article Nanomaterials are useful for their characteristic properties and are commonly used in various fields. Nanosized-magnetite (MGT) is widely utilized in medicinal and industrial fields, whereas their toxicological properties are not well documented. A safety assessment is thus urgently required for MGT, and genotoxicity is one of the most serious concerns. In the present study, we examined genotoxic effects of MGT using mice and revealed that DNA damage analyzed by a comet assay in the lungs of imprinting control region (ICR) mice intratracheally instilled with a single dose of 0.05 or 0.2 mg/animal of MGT was approximately two- to three-fold higher than that of vehicle-control animals. Furthermore, in gpt delta transgenic mice, gpt mutant frequency (MF) in the lungs of the group exposed to four consecutive doses of 0.2 mg MGT was significantly higher than in the control group. Mutation spectrum analysis showed that base substitutions were predominantly induced by MGT, among which G:C to A:T transition and G:C to T:A transversion were the most significant. To clarify the mechanism of mutation caused by MGT, we analyzed the formation of DNA adducts in the lungs of mice exposed to MGT. DNA was extracted from lungs of mice 3, 24, 72 and 168 h after intratracheal instillation of 0.2 mg/body of MGT, and digested enzymatically. 8-Oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG) and lipid peroxide-related DNA adducts were quantified by stable isotope dilution liquid chromatography-mass spectrometry (LC-MS/MS). Compared with vehicle control, these DNA adduct levels were significantly increased in the MGT-treated mice. In addition to oxidative stress- and inflammation related-DNA adduct formations, inflammatory cell infiltration and focal granulomatous formations were also observed in the lungs of MGT-treated mice. Based on these findings, it is suggested that inflammatory responses are probably involved in the genotoxicity induced by MGT in the lungs of mice. MDPI 2014-03-18 /pmc/articles/PMC5304606/ /pubmed/28348291 http://dx.doi.org/10.3390/nano4010175 Text en © 2014 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/).
spellingShingle Article
Totsuka, Yukari
Ishino, Kousuke
Kato, Tatsuya
Goto, Sumio
Tada, Yukie
Nakae, Dai
Watanabe, Masatoshi
Wakabayashi, Keiji
Magnetite Nanoparticles Induce Genotoxicity in the Lungs of Mice via Inflammatory Response
title Magnetite Nanoparticles Induce Genotoxicity in the Lungs of Mice via Inflammatory Response
title_full Magnetite Nanoparticles Induce Genotoxicity in the Lungs of Mice via Inflammatory Response
title_fullStr Magnetite Nanoparticles Induce Genotoxicity in the Lungs of Mice via Inflammatory Response
title_full_unstemmed Magnetite Nanoparticles Induce Genotoxicity in the Lungs of Mice via Inflammatory Response
title_short Magnetite Nanoparticles Induce Genotoxicity in the Lungs of Mice via Inflammatory Response
title_sort magnetite nanoparticles induce genotoxicity in the lungs of mice via inflammatory response
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5304606/
https://www.ncbi.nlm.nih.gov/pubmed/28348291
http://dx.doi.org/10.3390/nano4010175
work_keys_str_mv AT totsukayukari magnetitenanoparticlesinducegenotoxicityinthelungsofmiceviainflammatoryresponse
AT ishinokousuke magnetitenanoparticlesinducegenotoxicityinthelungsofmiceviainflammatoryresponse
AT katotatsuya magnetitenanoparticlesinducegenotoxicityinthelungsofmiceviainflammatoryresponse
AT gotosumio magnetitenanoparticlesinducegenotoxicityinthelungsofmiceviainflammatoryresponse
AT tadayukie magnetitenanoparticlesinducegenotoxicityinthelungsofmiceviainflammatoryresponse
AT nakaedai magnetitenanoparticlesinducegenotoxicityinthelungsofmiceviainflammatoryresponse
AT watanabemasatoshi magnetitenanoparticlesinducegenotoxicityinthelungsofmiceviainflammatoryresponse
AT wakabayashikeiji magnetitenanoparticlesinducegenotoxicityinthelungsofmiceviainflammatoryresponse