Simms Liam, Mason Elizabeth, Berg Ellen L, Yu Fan, Rudd Kathryn, Czekala Lukasz, Trelles Sticken Edgar, Brinster Oleg, Wieczorek Roman, Stevenson Matthew, Walele Tanvir
Imperial Brands PLC, 121 Winterstoke Road, Bristol BS3 2LL UK.
Eurofins Discovery, Inc., 111 Anza Blvd, Suite 414, Burlingame, CA 94010, USA.
Curr Res Toxicol. 2021 Aug 17;2:309-321. doi: 10.1016/j.crtox.2021.08.003. eCollection 2021.
A growing number of public health bodies, regulators and governments around the world consider electronic vapor products a lower risk alternative to conventional cigarettes. Of critical importance are rapid new approach methodologies to enable the screening of next generation products (NGPs) also known as next generation tobacco and nicotine products. In this study, the activity of conventional cigarette (3R4F) smoke and a range of NGP aerosols (heated tobacco product, hybrid product and electronic vapor product) captured in phosphate buffered saline, were screened by exposing a panel of human cell-based model systems using Biologically Multiplexed Activity Profiling (BioMAP® Diversity PLUS® Panel, Eurofins Discovery). Following exposure, the biological activity for a wide range of biomarkers in the BioMAP panel were compared to determine the presence of toxicity signatures that are associated with specific clinical findings. NGP aerosols were found to be weakly active in the BioMAP Diversity PLUS Panel (≤3/148 biomarkers) whereas significant activity was observed for 3R4F (22/148 biomarkers). Toxicity associated biomarker signatures for 3R4F included immunosuppression, skin irritation and thrombosis, with no toxicity signatures seen for the NGPs. BioMAP profiling could effectively be used to differentiate between complex mixtures of cigarette smoke or NGP aerosol extracts in a panel of human primary cell-based assays. Clinical validation of these results will be critical for confirming the utility of BioMAP for screening NGPs for potential adverse human effects.
全球越来越多的公共卫生机构、监管机构和政府认为，电子雾化产品是传统香烟风险较低的替代品。至关重要的是要有快速的新方法学，以便能够对下一代产品（NGP）进行筛查，下一代产品也被称为下一代烟草和尼古丁产品。在本研究中，通过使用生物多重活性分析（BioMAP® Diversity PLUS® Panel，欧陆科技集团发现部）对一组基于人类细胞的模型系统进行暴露，来筛查在磷酸盐缓冲盐水中捕获的传统卷烟（3R4F）烟雾和一系列NGP气溶胶（加热烟草产品、混合产品和电子雾化产品）的活性。暴露后，比较BioMAP分析组中多种生物标志物的生物活性，以确定与特定临床发现相关的毒性特征的存在。发现NGP气溶胶在BioMAP Diversity PLUS分析组中活性较弱（≤3/148种生物标志物），而3R4F则观察到显著活性（22/148种生物标志物）。3R4F的毒性相关生物标志物特征包括免疫抑制、皮肤刺激和血栓形成，而NGP未观察到毒性特征。在一组基于人类原代细胞的试验中，BioMAP分析可有效地用于区分香烟烟雾或NGP气溶胶提取物的复杂混合物。这些结果的临床验证对于确认BioMAP在筛查NGP潜在的对人类不良影响方面的效用至关重要。
