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

项目摘要 电子香烟（e-cigs），电池驱动的加热液体以产生吸入的气溶胶蒸汽的装置， 越来越受欢迎，尤其是在年轻用户中。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，对慢性吸烟引起的人类健康影响知之甚少。 暴露在这些烟雾中。越来越多的研究调查了电子烟对癌症的潜在风险， 呼吸道和心血管疾病。然而，来自我们实验室和其他实验室的新数据， 暴露于加热线圈金属丝释放的潜在神经毒性金属的人体健康问题， 其他电子烟组件。例如，我们发现，在我们收集的大部分电子烟气溶胶样本中， 镍、铬和铅的含量超过了EPA国家环境空气质量标准或ATSDR最低标准 风险水平（MRL）。值得注意的是，锰（Mn）是散发性帕金森病的主要嫌疑人， (PD)病因学其他人发现，钒，铜和硒（所有怀疑在PD的潜在作用） 与吸烟者相比，电子烟使用者的血液中的我们假设有害金属 电子烟释放的尼古丁可在大脑中积聚，并对神经退行性疾病造成重大的神经毒性风险。 慢性暴露的疾病。我们将从三个方面来检验我们的假设。首先，我们将确定 几种流行的电子烟在不同的环境下工作产生的气溶胶中可能含有神经毒性金属， 条件和具有不同风味和尼古丁含量的电子液体。第二，我们将研究神经毒素 慢性电子烟气溶胶暴露对来自携带者的人受试者的神经元细胞培养物的影响 与PD或健康对照相关的不完全渗透突变，并识别特定的金属混合物 神经毒性问题。第三，我们将测量长期暴露于电子烟的脑组织中的金属浓度。 小鼠，这是野生型对照或敲入突变，增加PD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。结果 这项研究可能会为决策者提供至关重要的、迄今为止无法获得的信息， 使他们能够评估二手接触电子烟气雾剂对健康造成的潜在神经毒性风险。 我们假设健康风险受到神经退行性疾病遗传易感性的显著影响， 疾病，以及电子烟装置构造、操作条件、电子液体调味剂和尼古丁含量。

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.