关键词： ACM, aerosol collected mass AhR, Aryl hydrocarbon receptor Alternative methods COPD, Chronic obstructive pulmonary disease EGFR, epidermal growth factor receptor ELISA, enzyme-linked immunosorbent assay EVP, Electronic vapor product HDFn, Human neonatal dermal fibroblasts HTP, Heated Tobacco Product HUVEC, Human umbilical vein endothelial cells HYB, Hybrid product containing e-liquid drawn through a tobacco plug IL, interleukin ISO, International Organization for Standardization In vitro assays MOA, Mechanism of action M−CSF, Macrophage colony-stimulating factor NGP, Next generation product NRC, National Research Council NRF2, Nuclear factor erythroid 2-related factor 2 Next generation products PBMC, Peripheral blood mononuclear cells PBS, Phosphate buffered saline Panel Phenotypic screening SRB, Sulforhodamine B TCR, T cell receptor TF, Tissue factor TLR, toll-like receptor TNFα, tumor necrosis factor alpha TPM, Total particulate matter Toxicity signature bPBS, Bubbled phosphate buffered saline mTOR, mechanistic target of rapamycin

来  源：   DOI：10.1016/j.crtox.2021.08.003   PDF(Sci-hub)   PDF(Pubmed)

Abstract：
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.
摘要：
越来越多的公共卫生机构，世界各地的监管机构和政府认为电子蒸汽产品是传统香烟的低风险替代品。至关重要的是快速的新方法方法，以筛选下一代产品（NGP），也称为下一代烟草和尼古丁产品。在这项研究中,传统香烟(3R4F)烟雾和一系列NGP气溶胶(加热烟草产品，混合产品和电子蒸汽产品)在磷酸盐缓冲盐水中捕获，通过使用BiologicallyMultiplexedActivityProfiling（BioMAP®DiversityPLUS®Panel，Eurofins发现）。曝光后，我们比较了BioMAP组中多种生物标志物的生物学活性,以确定是否存在与特定临床发现相关的毒性特征.在BioMAP多样性加上小组中发现NGP气溶胶的活性较弱（≤3/148个生物标志物），而在3R4F中观察到显着活性（22/148个生物标志物）。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，没有观察到NGP的毒性特征。在一组基于人原代细胞的测定中，BioMAP谱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用于筛选NGP的潜在人类不利影响的实用性至关重要。
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