A lower impact of an acute exposure to electronic cigarette aerosols than to cigarette smoke in human organotypic buccal and small airway cultures was demonstrated using systems toxicology assessment
A lower impact of an acute exposure to electronic cigarette aerosols than to cigarette smoke in human organotypic buccal and small airway cultures was demonstrated using systems toxicology assessment
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DOI：
10.1007/s11739-019-02055-x
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发表时间：
2019-09-01
影响因子：
4.6
通讯作者：
Hoeng, Julia
中科院分区：
文献类型：
--
作者：
Iskandar, Anita R.;Zanetti, Filippo;Hoeng, Julia
在烟草减害战略的背景下，应相对于香烟烟雾暴露的影响来评估电子烟（EC）暴露的潜在减少影响。我们进行了一系列体外研究，比较使用 MarkTen (R) EC 装置急性暴露于“测试混合物”（香料、尼古丁和保湿剂）、“基础”（尼古丁和保湿剂）和“载体”（保湿剂）配方的气溶胶的生物影响与暴露于匹配抽吸次数的 3R4F 参考香烟烟雾的影响，使用人体器官型气液界面口腔和小口。气道文化。每次暴露实验后，我们测量了暴露室中沉积的尼古丁和羰基化合物的浓度。沉积的羰基浓度用作评估潜在有毒挥发性物质暴露减少的代表性措施。我们遵循系统毒理学方法，通过多重和组学测定来补充功能生物学终点，例如组织病理学和纤毛跳动频率，以分别测量分泌的炎症蛋白和全基因组转录组。在分析的终点中，唯一对 EC 暴露表现出显着反应的参数是蛋白质和全基因组转录组的分泌。基于多重分析和组学分析，细胞对 EC 气溶胶暴露的反应具有组织类型特异性；然而，这些变化比接触香烟烟雾后的变化要小得多，即使在测试条件下接触 EC 气溶胶导致沉积的尼古丁浓度约为 EC 使用者唾液中尼古丁浓度的 200 倍。
In the context of tobacco harm-reduction strategy, the potential reduced impact of electronic cigarette (EC) exposure should be evaluated relative to the impact of cigarette smoke exposure. We conducted a series of in vitro studies to compare the biological impact of an acute exposure to aerosols of "test mix" (flavors, nicotine, and humectants), "base" (nicotine and humectants), and "carrier" (humectants) formulations using MarkTen (R) EC devices with the impact of exposure to smoke of 3R4F reference cigarettes, at a matching puff number, using human organotypic air-liquid interface buccal and small airway cultures. We measured the concentrations of nicotine and carbonyls deposited in the exposure chamber after each exposure experiment. The deposited carbonyl concentrations were used as representative measures to assess the reduced exposure to potentially toxic volatile substances. We followed a systems toxicology approach whereby functional biological endpoints, such as histopathology and ciliary beating frequency, were complemented by multiplex and omics assays to measure secreted inflammatory proteins and whole-genome transcriptomes, respectively. Among the endpoints analyzed, the only parameters that showed a significant response to EC exposure were secretion of proteins and whole-genome transcriptomes. Based on the multiplex and omics analyzes, the cellular responses to EC aerosol exposure were tissue type-specific; however, those alterations were much smaller than those following cigarette smoke exposure, even when the EC aerosol exposure under the testing conditions resulted in a deposited nicotine concentration approximately 200 times that in saliva of EC users.