Borghini Andrea, Roursgaard Martin, Andreassi Maria Grazia, Kermanizadeh Ali, Møller Peter
Genetics Unit, CNR Institute of Clinical Physiology, Via G. Moruzzi 1, 56124 Pisa, Pisa, Italy.
Department of Public Health, Section of Environmental Health, University of Copenhagen, Øster Farimagsgade 5A, DK-1014 Copenhagen, Denmark.
Mutagenesis. 2017 Jan;32(1):173-180. doi: 10.1093/mutage/gew036. Epub 2016 Aug 16.
One type of carbon nanotubes (CNTs) (MWCNT-7, from Mitsui) has been classified as probably carcinogenic to humans, however insufficient data does not warrant the same classification for other types of CNTs. Experimental data indicate that CNT exposure can result in oxidative stress and DNA damage in cultured cells, whereas these materials appear to induce low or no mutagenicity. Therefore, the present study aimed to investigate whether in vitro exposure of cultured airway epithelial cells (A549) to multi-walled CNTs (MWCNTs) could increase the DNA repair activity of oxidatively damaged DNA and drive the cells toward replicative senescence, assessed by attrition of telomeres. To investigate this, HO and KBrO were used to induce DNA damage in the cells and the effect of pre-exposure to MWCNT tested for a change in repair activity inside the cells or in the extract of treated cells. The effect of MWCNT exposure on telomere length was investigated for concentration and time response. We report a significantly increased repair activity in A549 cells exposed to MWCNTs compared to non-exposed cells, suggesting that DNA repair activity may be influenced by exposure to MWCNTs. The telomere length was decreased at times longer than 24h, but this decrease was not concentration dependent. The results suggest that the seemingly low mutagenicity of CNTs in cultured cells may be associated with an increased DNA repair activity and a replicative senescence, which may counteract the manifestation of DNA lesions to mutations.
一种碳纳米管（CNTs）（MWCNT - 7，来自三井公司）已被归类为可能对人类致癌，然而，数据不足无法对其他类型的碳纳米管进行同样的分类。实验数据表明，接触碳纳米管可导致培养细胞中的氧化应激和DNA损伤，而这些材料似乎诱导低诱变活性或无诱变活性。因此，本研究旨在调查培养的气道上皮细胞（A549）在体外接触多壁碳纳米管（MWCNTs）是否会增加氧化损伤DNA的修复活性，并通过端粒损耗评估使细胞走向复制性衰老。为了研究这一点，使用过氧化氢（HO）和溴酸钾（KBrO）诱导细胞中的DNA损伤，并测试预先接触MWCNT对细胞内或处理细胞提取物中修复活性变化的影响。研究了MWCNT暴露对端粒长度的浓度和时间响应效应。我们报告，与未接触的细胞相比，接触MWCNTs的A549细胞的修复活性显著增加，这表明DNA修复活性可能受接触MWCNTs的影响。在超过24小时时端粒长度缩短，但这种缩短不依赖于浓度。结果表明，碳纳米管在培养细胞中看似低的诱变活性可能与DNA修复活性增加和复制性衰老有关，这可能抵消DNA损伤向突变的表现。
