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降低多壁碳纳米管遗传毒性和肺部炎症的安全设计策略:长度的减少和 COOH 基团的引入。

Safe-by-design strategies for lowering the genotoxicity and pulmonary inflammation of multiwalled carbon nanotubes: Reduction of length and the introduction of COOH groups.

机构信息

National Research Centre for the Working Environment (NFA), 105 Lersø Parkallé, Copenhagen Ø, Denmark.

INAC (Institute for Nanoscience and Cryogenics), LAN (Laboratoire Lésions des Acides Nucléiques, Nucleic Acid Lesions Laboratory), 17 Avenue des Martyrs, 38054, Grenoble Cedex 09, France.

出版信息

Environ Toxicol Pharmacol. 2021 Oct;87:103702. doi: 10.1016/j.etap.2021.103702. Epub 2021 Jul 10.

DOI:10.1016/j.etap.2021.103702
PMID:34252584
Abstract

Potentially, the toxicity of multiwalled carbon nanotubes (MWCNTs) can be reduced in a safe-by-design strategy. We investigated if genotoxicity and pulmonary inflammation of MWCNTs from the same batch were lowered by a) reducing length and b) introducing COOH-groups into the structure. Mice were administered: 1) long and pristine MWCNT (CNT-long) (3.9 μm); 2) short and pristine CNT (CNT-short) (1 μm); 3) CNT modified with high ratio COOH-groups (CNT-COOH-high); 4) CNT modified with low ratio COOH-groups (CNT-COOH-low). MWCNTs were dosed by intratracheal instillation at 18 or 54 μg/mouse (∼0.9 and 2.7 mg/kg bw). Neutrophils numbers were highest after CNT-long exposure, and both shortening the MWCNT and addition of COOH-groups lowered pulmonary inflammation (day 1 and 28). Likewise, CNT-long induced genotoxicity, which was absent with CNT-short and after introduction of COOH groups. In conclusion, genotoxicity and pulmonary inflammation of MWCNTs were lowered, but not eliminated, by shortening the fibres or introducing COOH-groups.

摘要

多壁碳纳米管(MWCNTs)的毒性在安全设计策略中可能会降低。我们研究了同一批次的 MWCNTs 的长度变短和结构中引入 COOH 基团是否会降低其遗传毒性和肺部炎症。给小鼠分别施用以下物质:1)长而原始的 MWCNT(CNT-long)(3.9 μm);2)短而原始的 CNT(CNT-short)(1 μm);3)高比例 COOH 基团修饰的 CNT(CNT-COOH-high);4)低比例 COOH 基团修饰的 CNT(CNT-COOH-low)。MWCNTs 通过气管内滴注的方式给药,剂量为 18 或 54 μg/只小鼠(约 0.9 和 2.7 mg/kg bw)。CNT-long 暴露后中性粒细胞数量最高,MWCNT 变短和添加 COOH 基团均可降低肺部炎症(第 1 天和第 28 天)。同样,CNT-long 诱导了遗传毒性,而 CNT-short 和引入 COOH 基团后则没有。总之,MWCNTs 的遗传毒性和肺部炎症通过纤维变短或引入 COOH 基团降低,但并未完全消除。

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