Single versus repeated exposure to human polarized intestinal epithelial monolayers for in vitro protein hazard characterization.

Autor: Lanter BB; Department of Pediatrics, Mucosal Immunology & Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114, United States., Eaton AD; Department of Pediatrics, Mucosal Immunology & Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114, United States., Roper JM; Corteva Agriscience, Newark, DE, 19711, United States., Zimmermann C; Corteva Agriscience, Johnston, IA, 50131, United States. Electronic address: cindi.zimmermann@corteva.com., Delaney B; Corteva Agriscience, Johnston, IA, 50131, United States., Hurley BP; Department of Pediatrics, Mucosal Immunology & Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114, United States. Electronic address: bphurley@mgh.harvard.edu.
Jazyk: angličtina
Zdroj: Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association [Food Chem Toxicol] 2019 Oct; Vol. 132, pp. 110666. Date of Electronic Publication: 2019 Jul 06.
DOI: 10.1016/j.fct.2019.110666
Abstrakt: Recent studies suggest human-derived intestinal epithelial cell (IEC) lines cultured as polarized monolayers on permeable Transwell ® filters are effective at differentiating between hazardous and non-hazardous proteins following a single exposure. In this study, IEC polarized monolayers were subjected to hazardous or non-hazardous proteins in nine exposures over 30 days and compared to a single exposure of the same protein. The objective was to evaluate whether repeated exposures to a protein differently alter barrier integrity or compromise cell viability compared to single exposures. Proteins tested included Clostridium difficile toxin A, Streptolysin O, Wheat Germ Agglutinin, Phaseolus vulgaris Hemagglutinin-E, bovine serum albumin, porcine serum albumin, and fibronectin. Evidence of diminished barrier integrity and/or cell viability following exposure to hazardous proteins was more pronounced in magnitude when IECs were subjected to multiple rather than single exposures. In some cases, an effect on IEC monolayers was observed only with repeated exposures. In general, IEC responses to non-hazardous proteins following either single or repeated exposures were minimal. Results from these studies support the utility of using cultured human IEC polarized monolayers to differentiate between hazardous and non-hazardous proteins and suggest that repeated exposures may reveal a greater magnitude of response when compared to single exposures.
(Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)
Databáze: MEDLINE