The biological effects of long-term exposure of human bronchial epithelial cells to total particulate matter from a candidate modified-risk tobacco product. (August 2018)

• Record Type: Journal Article
• Authors: van der Toorn, Marco; Sewer, Alain; Marescotti, Diego; Johne, Stephanie; Baumer, Karin; Bornand, David; Dulize, Remi; Merg, Celine; Corciulo, Maica; Scotti, Elena; Pak, Claudius; Leroy, Patrice; Guedj, Emmanuel; Ivanov, Nikolai; Martin, Florian; Peitsch, Manuel; Hoeng, Julia; Luettich, Karsta
• Is Part Of: Toxicology in vitro. Volume 50(2018)
• Page Start: 95
• Page End: 108
• Publication Date: 2018-08
• Subjects: A.U. Arbitrary units -- BEBM Bronchial epithelial cell basal medium -- BEGM Bronchial epithelial cell growth medium -- BIF Biological impact factor -- CCL5 Chemokine (C-C motif) ligand 5 -- CDH1 Cadherin-1 -- CFA Cell fate network -- CIM Cell invasion migration -- cMRTP Candidate modified-risk tobacco product -- COPD Chronic obstructive pulmonary disease -- CPR Cell proliferation network -- CSF-2 Colony-stimulating factor 2 -- CSF-3 Colony-stimulating factor 3 -- CTNNB1 Catenin beta 1 -- CO2 Carbon dioxide -- cRNA Complementary RNA -- CS Cigarette smoke -- CST Cellular stress network -- CXCL-1 Chemokine (C-X-C motif) ligand 1 -- CXCL-5 Chemokine (C-X-C motif) ligand 1 -- DDR DNA damage response -- DNA Deoxyribonucleic acid -- DHE Dihydroethidium -- DMSO Dimethyl sulfoxide -- FCS Fetal calf serum -- FDA Food and Drug Administration -- FDR False discovery rate -- fRMA Frozen robust microarray analysis -- GC Gas chromatography -- GSH Glutathione -- EDTA Ethylene diaminetetraacetic acid -- EMT Epithelial-mesenchymal transition -- FDA Food and Drug Administration -- FDR False discovery rate -- FID Flame ionization detection -- H2AX Histone 2AX -- pH2AX Phosphorylation histone 2AX -- γH2AX Gamma histone 2AX -- HCS High content screening -- HECD-1 Mouse monoclonal E Cadherin antibody -- HPHC Harmful and potentially harmful constituents -- IL-1A Interleukin-1 alfa -- IL-1B Interleukin-1 beta -- IL-8 Interleukin-8 -- IPA Ingenuity pathway analysis -- IPN Inflammatory process network -- KEGG Kyoto Encyclopedia of Genes and Genomes -- LC Lung cancer -- mBCL Monochlorobimane -- MET Mesenchymal-epithelial transition -- miRNA micro Ribonucleic acid -- mRNA messenger Ribonucleic acid -- MMP Matrix metalloproteinase -- ND Not determined -- NHBE Normal human bronchial epithelial -- NPA Network perturbation amplitude -- NUSE Normalized unscaled standard error -- RBIF Relative biological impact factor -- RMA Robust multi-array -- RNA Ribonucleic acid -- rpm Rounds per minute -- RTCA-DP Real-time cell analyzer dual-plate -- RTCA-MP Real-time cell analyzer multi-plate -- RLE Relative log expression -- RNA Ribonucleic acid -- ROS Reactive oxygen species -- SDC2 Syndecan-2 -- SEM Standard error of the mean -- TAGLN Transgelin -- TGF-β Transforming growth factor beta -- THS Tobacco Heating System -- TIMP Tissue inhibitor of metalloproteinase -- TPM Total particulate matter -- TPM1 Tropomyosin alpha-1 chain -- TRA Tissue repair and angiogenesis -- VEGF Vascular endothelial growth factor -- VEGFA Vascular endothelial growth factor A -- VIM Vimentin; Lung cancer -- Epithelium -- Cigarette -- Tobacco heating system -- Modified-risk tobacco product; Toxicity testing -- In vitro -- Periodicals; Toxicology -- Periodicals; 615.9
• DOI: 10.1016/j.tiv.2018.02.019
• Languages: English
• ISSNs: 0887-2333

Abstract

Abstract: Cigarette smoking is the leading cause of preventable lung cancer (LC). Reduction of harmful constituents by heating rather than combusting tobacco may have the potential to reduce the risk of LC. We evaluated functional and molecular changes in human bronchial epithelial BEAS-2B cells following a 12-week exposure to total particulate matter (TPM) from the aerosol of a candidate modified-risk tobacco product (cMRTP) in comparison with those following exposure to TPM from the 3R4F reference cigarette. Endpoints linked to lung carcinogenesis were assessed. Four-week 3R4F TPM exposure resulted in crisis and epithelial to mesenchymal transition (EMT) accompanied by decreased barrier function and disrupted cell-to-cell contacts. By week eight, cells regained E-cadherin expression, suggesting that EMT was reversible. Increased levels of inflammatory mediators were noted in cells treated to 3R4F TPM but not in cells treated to the same or a five-fold higher concentration of cMRTP TPM. A 20-fold higher concentration of cMRTP TPM increased oxidative stress and DNA damage and caused reversible EMT. Anchorage-independent growth was observed in cells treated to 3R4F or a high concentration of cMRTP TPM. 3R4F TPM-derived clones were invasive, while cMRTP TPM-derived clones were not. Long-term exposure to TPM from the cMRTP had a lower biological impact on BEAS-2B cells compared with that of exposure to TPM from 3R4F. Highlights: A cellular model featuring chronic exposure may be a suitable in vitro approach for cancer risk assessment. Short-term exposure to tobacco product TPM resulted in cellular crisis and EMT. Long-term exposure to tobacco product TPM resulted in cellular transformation. TPM from THS2.2 had a lower biological impact then TPM from 3R4F. Heating rather than combusting tobacco may reduce the risk of lung cancer.