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

View Article: PubMed Central - PubMed

ABSTRACT

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.

No MeSH data available.


Related in: MedlinePlus

The gpt mutation frequencies in the lungs of mice after multiple intratracheal instillations of MGT. Male mice were treated with multiple (0.05 or 0.2 mg/mouse × 4 times) doses of MGT, and mice were sacrificed eight weeks after MGT administration. The data represent the mean ± SD; *P < 0.05 by the Student’s t-test vs. the corresponding vehicle control mice.
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nanomaterials-04-00175-f003: The gpt mutation frequencies in the lungs of mice after multiple intratracheal instillations of MGT. Male mice were treated with multiple (0.05 or 0.2 mg/mouse × 4 times) doses of MGT, and mice were sacrificed eight weeks after MGT administration. The data represent the mean ± SD; *P < 0.05 by the Student’s t-test vs. the corresponding vehicle control mice.

Mentions: All mice in this study behaved normally and survived throughout the experimental period. The treated animals did not show fatigue, loss of appetite or weight loss. Figure 3 shows gpt mutant frequencies (MFs) in the lungs of gpt delta transgenic mice exposed to four consecutive intratracheal instillations of 0.05 mg or 0.2 mg MGT.


Magnetite Nanoparticles Induce Genotoxicity in the Lungs of Mice via Inflammatory Response
The gpt mutation frequencies in the lungs of mice after multiple intratracheal instillations of MGT. Male mice were treated with multiple (0.05 or 0.2 mg/mouse × 4 times) doses of MGT, and mice were sacrificed eight weeks after MGT administration. The data represent the mean ± SD; *P < 0.05 by the Student’s t-test vs. the corresponding vehicle control mice.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5304606&req=5

nanomaterials-04-00175-f003: The gpt mutation frequencies in the lungs of mice after multiple intratracheal instillations of MGT. Male mice were treated with multiple (0.05 or 0.2 mg/mouse × 4 times) doses of MGT, and mice were sacrificed eight weeks after MGT administration. The data represent the mean ± SD; *P < 0.05 by the Student’s t-test vs. the corresponding vehicle control mice.
Mentions: All mice in this study behaved normally and survived throughout the experimental period. The treated animals did not show fatigue, loss of appetite or weight loss. Figure 3 shows gpt mutant frequencies (MFs) in the lungs of gpt delta transgenic mice exposed to four consecutive intratracheal instillations of 0.05 mg or 0.2 mg MGT.

View Article: PubMed Central - PubMed

ABSTRACT

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&prime;-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.

No MeSH data available.


Related in: MedlinePlus