Thirdhand smoke causes DNA damage in human cells
Thirdhand smoke causes DNA damage in human cells
复制标题
DOI：
10.1093/mutage/get013
复制
发表时间：
2013-07-01
期刊：
影响因子：
2.7
通讯作者：
Gundel, Lara A.
中科院分区：
文献类型：
--
作者：
Hang, Bo;Sarker, Altaf H.;Gundel, Lara A.
暴露于三手烟(THS)是一种新的健康风险。有证据支持它在室内环境中的广泛存在。然而，它的遗传毒性潜力，这是风险评估的一个关键方面，几乎没有经过测试。THS的一个重要特征是其在老化过程中经历化学转化的能力，最近的一项研究表明，吸附的尼古丁与室内污染物亚硝酸反应生成烟草特有的亚硝胺，如4-(甲基亚硝氨基)-4-(3-吡啶)丁醛(NNA)和4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone(NNK)。这项研究的目的是使用两种体外试验来评估THS对人类细胞株的遗传毒性。这是在模拟短期(急性)和长期(慢性)暴露的实验室系统中产生的。用液相色谱-串联质谱法对吸附在纤维素底物上的THS提取物中的TSNAs和常见的烟草生物碱进行了定量。人肝癌细胞暴露于急性或慢性THS 24小时后，在碱性彗星试验中DNA链断裂显著增加。在同一检测中，单独暴露于NNA的细胞培养显示出显著更高的DNA损伤水平。在新排放的二手烟中不存在NNA，但它是吸烟发生很长时间后尼古丁与HONO反应时在THS中形成的主要TSNA。大片段定量聚合酶链式反应检测到，与未经处理的细胞相比，慢性THS暴露24小时后，培养的人细胞中次黄嘌呤磷酸核糖转移酶1(HPRT)和聚合酶(POLB)基因的氧化损伤水平显著增加，提示THS暴露与氧化应激增加有关，可能是THS介导的毒性的重要因素。这项研究的结果首次表明，暴露于THS对人类细胞系具有遗传毒性。
Exposure to thirdhand smoke (THS) is a newly described health risk. Evidence supports its widespread presence in indoor environments. However, its genotoxic potential, a critical aspect in risk assessment, is virtually untested. An important characteristic of THS is its ability to undergo chemical transformations during aging periods, as demonstrated in a recent study showing that sorbed nicotine reacts with the indoor pollutant nitrous acid (HONO) to form tobacco-specific nitrosamines (TSNAs) such as 4-(methylnitrosamino)-4-(3-pyridyl)butanal (NNA) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). The goal of this study was to assess the genotoxicity of THS in human cell lines using two in vitro assays. THS was generated in laboratory systems that simulated short (acute)- and long (chronic)-term exposures. Analysis by liquid chromatographytandem mass spectrometry quantified TSNAs and common tobacco alkaloids in extracts of THS that had sorbed onto cellulose substrates. Exposure of human HepG2 cells to either acute or chronic THS for 24h resulted in significant increases in DNA strand breaks in the alkaline Comet assay. Cell cultures exposed to NNA alone showed significantly higher levels of DNA damage in the same assay. NNA is absent in freshly emitted secondhand smoke, but it is the main TSNA formed in THS when nicotine reacts with HONO long after smoking takes place. The long ampliconquantitative PCR assay quantified significantly higher levels of oxidative DNA damage in hypoxanthine phosphoribosyltransferase 1 (HPRT) and polymerase (POLB) genes of cultured human cells exposed to chronic THS for 24h compared with untreated cells, suggesting that THS exposure is related to increased oxidative stress and could be an important contributing factor in THS-mediated toxicity. The findings of this study demonstrate for the first time that exposure to THS is genotoxic in human cell lines.