PMI R&D, Philip Morris Products S.A., Part of Philip Morris International group of companies, Quai Jeanrenaud 5, CH-2000 Neuchâtel, Switzerland.
PMI R&D, Philip Morris Products S.A., Part of Philip Morris International group of companies, Quai Jeanrenaud 5, CH-2000 Neuchâtel, Switzerland.
Food Chem Toxicol. 2018 May;115:109-126. doi: 10.1016/j.fct.2018.02.063. Epub 2018 Mar 1.
The biological impact of an aerosol of a potential modified-risk tobacco product, carbon heated tobacco product 1.2 (CHTP1.2), was comprehensively assessed for the first time in vitro using human small airway and nasal epithelial models following a systems toxicology approach. The potentially reduced effects of CHTP1.2 aerosol exposure were benchmarked against those of 3R4F cigarette smoke at similar nicotine concentrations. Experimental repetitions were conducted for which new batches of small airway and nasal cultures were exposed to CHTP1.2 aerosol or 3R4F smoke for 28 minutes. The biological impacts were determined based on a collection of endpoints including morphology, cytotoxicity, proinflammatory mediator profiles, cytochrome P450 1A1/1B1 activity, global mRNA and microRNA changes and proteome profiles. Alterations in mRNA expression were detected in cultures exposed to CHTP1.2 aerosol, without noticeable morphological changes and cytotoxicity, and minimal impact on proinflammatory mediator and proteome profiles. The changes linked to CHTP1.2 aerosol exposure, when observed, were transient. However, the impact of 3R4F smoke exposure persisted long post-exposure and greater than CHTP1.2 aerosol. Morphological changes were observed only in cultures exposed to 3R4F smoke. The lower biological effects of CHTP1.2 aerosol than 3R4F smoke exposure were observed similarly in both small airway and nasal epithelial cultures.
首次采用系统毒理学方法，在体外全面评估了潜在减害烟草制品气溶胶（加热不燃烧烟草制品 1.2 型，CHTP1.2）对人小气道和鼻腔上皮细胞模型的生物学影响，并将其与具有相似尼古丁浓度的 3R4F 卷烟烟雾的潜在降低作用进行了基准比较。对新批次的小气道和鼻腔培养物进行了实验重复，使其暴露于 CHTP1.2 气溶胶或 3R4F 烟雾中 28 分钟。根据一系列终点来确定生物学影响，包括形态、细胞毒性、促炎介质谱、细胞色素 P450 1A1/1B1 活性、全局 mRNA 和 microRNA 变化以及蛋白质组谱。暴露于 CHTP1.2 气溶胶的培养物中检测到 mRNA 表达的改变，没有明显的形态变化和细胞毒性，对促炎介质和蛋白质组谱的影响最小。与 CHTP1.2 气溶胶暴露相关的变化是短暂的。然而，3R4F 烟雾暴露的影响在暴露后持续时间较长，且大于 CHTP1.2 气溶胶。仅在暴露于 3R4F 烟雾的培养物中观察到形态变化。在小气道和鼻腔上皮细胞培养物中，均观察到 CHTP1.2 气溶胶的生物学效应低于 3R4F 烟雾暴露。
