Neurotoxic and neurodegenerative risks from chronic exposure to metal mixtures in e-cigarette aerosol

项目总结 电子烟(e-cig)，加热液体以产生吸入气雾剂蒸汽的电池驱动装置， 越来越受欢迎，特别是在年轻用户中。电子烟被视为一种越来越有吸引力的 烟草香烟的替代品；然而，人们对长期吸烟对人类健康的影响知之甚少 暴露在这些气雾剂中。越来越多的研究研究了电子烟对癌症的潜在风险， 呼吸系统疾病和心血管疾病。然而，来自我们实验室和其他实验室的新数据提出了额外的 人类健康担忧暴露于从加热的线圈线释放出的潜在神经毒性金属和 其他电子烟组件。例如，我们发现，在我们收集的一大部分电子烟气溶胶样本中， 镍、铬和铅的水平超过了EPA国家环境空气质量标准或ATSDR的最低标准 风险水平(MRL)。值得注意的是，散发性帕金森氏症的主要嫌疑人--锰(Mn)也是如此 (PD)病因学。其他人发现，钒、铜和硒(都被怀疑在帕金森氏病中起到了潜在作用) 与吸烟者相比，电子烟使用者的血液中含量更高。我们假设危险金属 电子烟释放的物质可能会在大脑中积累，并对神经退行性变构成重大的神经毒性风险(S) 因长期接触而引发的疾病。我们将通过三种方式检验我们的假设。首先，我们将确定级别 由几种流行的电子烟在不同的操作条件下产生的气溶胶中潜在的神经毒性金属 条件和电子液体的味道和尼古丁含量不同。第二，我们将检测神经毒性 慢性e-CIG气溶胶暴露对人神经细胞培养的影响 与帕金森病或健康对照有关的不完全穿透性突变，并鉴定特定的金属混合物 神经毒性问题。第三，我们将测量长期接触电子烟的脑组织中的金属浓度。 老鼠，它们是野生型对照或敲击突变，增加了患帕金森病的风险；我们还将 在小鼠模型中确定金属对运动功能和认知的潜在不利影响。发现 这项研究可能会向政策制定者提供关键的和迄今无法获得的信息，并将 使他们能够评估二手接触电子烟气雾剂可能产生的神经毒性健康风险。 我们假设，神经退行性变的遗传易感性对健康风险有显著影响。 疾病，以及电子烟设备结构、操作条件、电子液体调味料和尼古丁含量。

PROJECT SUMMARY Electronic cigarettes (e-cigs), battery-operated devices that heat liquids to generate an inhaled aerosol vapor, are increasingly popular, especially among younger users. E-cigs are seen as an increasingly attractive alternative to tobacco cigarettes; however, little is known about the human health effects arising from chronic exposure to these aerosols. A growing number of studies have examined potential e-cig risks for cancer, respiratory, and cardiovascular diseases. New data from our laboratory and others, however, raise additional human health concerns about exposure to potentially neurotoxic metals released from the heated coil wire and other e-cig components. For example, we found that in a large fraction e-cig aerosol samples we collected, nickel, chromium, and lead levels exceeded EPA national ambient air quality standards or ATSDR minimum risk levels (MRL). Notably, this was true for manganese (Mn), a prime suspect in sporadic Parkinson’s disease (PD) etiology. Others have found that vanadium, copper and selenium (all suspected for a potential role in PD) were higher in blood of e-cig users as compared to tobacco smokers. We hypothesize that hazardous metals released by e-cigs may accumulate in the brain and pose significant neurotoxic risk(s) for neurodegenerative diseases upon chronic exposure. We will test our hypothesis in three ways. First, we will determine the levels of potentially neurotoxic metals in the aerosol produced by several popular e-cigs operated under different conditions and with e-liquids differing in flavor and nicotine content. Second, we will examine the neurotoxic effect of chronic e-cig aerosol exposure in neuronal cell cultures derived from human subjects carrying incompletely-penetrant mutations linked to PD or from healthy controls, and identify metal mixtures of particular neurotoxic concern. Third, we will measure metal concentrations in brain tissue of chronically e-cig exposed mice, which are wildtype controls or knock-in for a mutation that increases the risk for PD; we will also determine the metals’ potential adverse effects on motor function and cognition in the mouse models. Findings from this study are likely to provide crucial and heretofore unavailable information to policy makers and will enable them to evaluate potential neurotoxic health risks arising from second-hand exposure to e-cig aerosol. We hypothesize that health risks are significantly influenced by genetic susceptibility to neurodegenerative disease, as well as by e-cig device construction, operating conditions, e-liquid flavoring, and nicotine content.