The use of human induced pluripotent stem cells to screen for developmental toxicity potential indicates reduced potential for non-combusted products, when compared to cigarettes.

Autor:	Simms L; Imperial Brands PLC, 121 Winterstoke Road, Bristol BS3 2LL, UK., Rudd K; Imperial Brands PLC, 121 Winterstoke Road, Bristol BS3 2LL, UK., Palmer J; Stemina Biomarker Discovery Inc., 504 S. Rosa Rd., Madison, WI 53719, USA., Czekala L; Imperial Brands PLC, 121 Winterstoke Road, Bristol BS3 2LL, UK., Yu F; Imperial Brands PLC, 121 Winterstoke Road, Bristol BS3 2LL, UK., Chapman F; Imperial Brands PLC, 121 Winterstoke Road, Bristol BS3 2LL, UK., Trelles Sticken E; Reemtsma Cigarettenfabriken GmbH, An Imperial Brands PLC Company, Albert-EinsteinRing-7, D-22761 Hamburg, Germany., Wieczorek R; Reemtsma Cigarettenfabriken GmbH, An Imperial Brands PLC Company, Albert-EinsteinRing-7, D-22761 Hamburg, Germany., Bode LM; Reemtsma Cigarettenfabriken GmbH, An Imperial Brands PLC Company, Albert-EinsteinRing-7, D-22761 Hamburg, Germany., Stevenson M; Imperial Brands PLC, 121 Winterstoke Road, Bristol BS3 2LL, UK., Walele T; Imperial Brands PLC, 121 Winterstoke Road, Bristol BS3 2LL, UK.
Jazyk:	angličtina
Zdroj:	Current research in toxicology [Curr Res Toxicol] 2020 Nov 15; Vol. 1, pp. 161-173. Date of Electronic Publication: 2020 Nov 15 (Print Publication: 2020).
DOI:	10.1016/j.crtox.2020.11.001
Abstrakt:	devTOX quick Predict (devTOX qP ) is a metabolomics biomarker-based assay that utilises human induced pluripotent stem (iPS) cells to screen for potential early stage embryonic developmental toxicity in vitro. Developmental toxicity potential is assessed based on the assay endpoint of the alteration in the ratio of key unrelated biomarkers, ornithine and cystine (o/c). This work aimed to compare the developmental toxicity potential of tobacco-containing and tobacco-free non-combustible nicotine products to cigarette smoke. Smoke and aerosol from test articles were produced using a Vitrocell VC10 smoke/aerosol exposure system and bubbled into phosphate buffered saline (bPBS). iPS cells were exposed to concentrations of up to 10% bPBS. Assay sensitivity was assessed through a spiking study with a known developmental toxicant, all -trans- retinoic acid (ATRA), in combination with cigarette smoke extract. The bPBS extracts of reference cigarettes (1R6F and 3R4F) and a heated tobacco product (HTP) were predicted to have the potential to induce developmental toxicity, in this screening assay. The bPBS concentration at which these extracts exceeded the developmental toxicity threshold was 0.6% (1R6F), 1.3% (3R4F), and 4.3% (HTP) added to the cell media. Effects from cigarette smoke and HTP aerosol were driven largely by cytotoxicity, with the cell viability and o/c ratio dose-response curves crossing the developmental toxicity thresholds at very similar concentrations of added bPBS. The hybrid product and all the electronic cigarette (e-cigarette) aerosols were not predicted to be potential early developmental toxicants, under the conditions of this screening assay. Competing Interests: The mybluTM devices used in this study were manufactured by Fontem Ventures B.V., a wholly owned subsidiary of Imperial Brands. All the authors were employed by Imperial Brands PLC or subsidiaries at time of writing, these were Simms, L., Rudd, K., Czekala, L., Yu, F., Chapman, F., Trelles-Sticken, E., Wieczorek, R., Bode, L., Stevenson, M., Walele, T. (© 2020 The Authors.)
Databáze:	MEDLINE
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