Genotoxicity of multi-walled carbon nanotubes in both in vitro and in vivo assay systems
Genotoxicity of multi-walled carbon nanotubes in both in vitro and in vivo assay systems
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DOI：
10.3109/17435390.2012.674571
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发表时间：
2013-06-01
期刊：
影响因子：
5
通讯作者：
Wakabayashi, Keiji
中科院分区：
文献类型：
--
作者：
Kato, Tatsuya;Totsuka, Yukari;Wakabayashi, Keiji
采用体外和体内实验研究了多壁碳纳米管（MWCNTs）的遗传毒性效应。多壁碳纳米管显著诱导A549细胞微核，并增加CHO AA 8细胞姐妹染色单体交换（SCE）频率。当ICR小鼠气管内滴注单剂量（0.05或0.2毫克/动物）的多壁碳纳米管，DNA损伤的肺，彗星试验分析，以剂量依赖性的方式增加。此外，DNA氧化损伤，表明8-氧代-7，8-二氢-2 '-脱氧鸟苷和庚酮乙烯脱氧核糖核苷，发生在肺的MWCNT暴露小鼠。多壁碳纳米管处理的gpt δ转基因小鼠的肺中gpt突变频率显著增加。颠换占主导地位，和G：C到C：G明显增加多壁碳纳米管。此外，在MWCNT暴露小鼠的肺中观察到诱导型NO合酶和硝基酪氨酸的化学染色的许多区域。总体而言，多壁碳纳米管在体外和体内试验中均显示出遗传毒性;其机制可能涉及氧化应激和炎症反应。
The genotoxic effects of multi-walled carbon nanotubes (MWCNTs) were examined by using in vitro and in vivo assays. MWCNTs significantly induced micronuclei in A549 cells and enhanced the frequency of sister chromatid exchange (SCE) in CHO AA8 cells. When ICR mice were intratracheally instilled with a single dose (0.05 or 0.2 mg/animal) of MWCNTs, DNA damage of the lungs, analysed by comet assay, increased in a dose-dependent manner. Moreover, DNA oxidative damage, indicated by 8-oxo-7,8-dihydro-2'-deoxyguanosine and heptanone etheno-deoxyribonucleosides, occurred in the lungs of MWCNT-exposed mice. The gpt mutation frequencies significantly increased in the lungs of MWCNT-treated gpt delta transgenic mice. Transversions were predominant, and G: C to C: G was clearly increased by MWCNTs. Moreover, many regions immunohistochemically stained for inducible NO synthase and nitrotyrosine were observed in the lungs of MWCNT-exposed mice. Overall, MWCNTs were shown to be genotoxic both in in vitro and in vivo tests; the mechanisms probably involve oxidative stress and inflammatory responses.