title: Diacetyl and 2,3-pentanedione exposure of human cultured airway epithelial cells: Ion transport effects and metabolism of butter flavoring agents.
abstract: Inhalation of butter flavoring by workers in the microwave popcorn industry may result in “popcorn workers' lung.” In previous in vivo studies rats exposed for 6 h to vapor from the flavoring agents, diacetyl and 2,3-pentanedione, acquired flavoring concentration-dependent damage of the upper airway epithelium and airway hyporeactivity to inhaled methacholine. Because ion transport is essential for lung fluid balance,we hypothesized that alterations in ion transport may be an early manifestation of butter flavoring-induced toxicity.We developed a system to expose cultured human bronchial/tracheal epithelial cells (NHBEs) to flavoring vapors. NHBEs were exposed for 6 h to diacetyl or 2,3-pentanedione vapors (25 or ≥ 60 ppm) and the effects on short circuit current and transepithelial resistance (Rt) were measured. Immediately after exposure to 25 ppm both flavorings reduced Na+ transport,without affecting Cl- transport or Na+,K+-pump activity. Rt was unaffected. Na+ transport recovered 18 h after exposure. Concentrations (100-360 ppm) of diacetyl and 2,3-pentanedione reported earlier to give rise in vivo to epithelial damage, and 60 ppm, caused death of NHBEs 0 h post-exposure. Analysis of the basolateral medium indicated that NHBEs metabolize diacetyl and 2,3-pentanedione to acetoin and 2-hydroxy-3-pentanone, respectively. The results indicate that ion transport is inhibited transiently in airway epithelial cells by lower concentrations of the flavorings than those that result in morphological changes of the cells in vivo or in vitro.
authors.affiliation: Department of Pharmaceutical Sciences, West Virginia University, Morgantown, WV, USA.
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Zaccone
authors.affiliation: Pathology and Physiology Research Branch, National Institute for Occupational Safety and Health, Morgantown, WV, USA.
authors.forename: W Travis
authors.initials: WT
authors.lastname: Goldsmith
authors.affiliation: Department of Pharmaceutical Sciences, West Virginia University, Morgantown, WV, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Shimko
authors.affiliation: Pathology and Physiology Research Branch, National Institute for Occupational Safety and Health, Morgantown, WV, USA.
authors.forename: J R
authors.initials: JR
authors.lastname: Wells
authors.affiliation: Pathology and Physiology Research Branch, National Institute for Occupational Safety and Health, Morgantown, WV, USA.
authors.forename: Diane
authors.initials: D
authors.lastname: Schwegler-Berry
authors.affiliation: Pathology and Physiology Research Branch, National Institute for Occupational Safety and Health, Morgantown, WV, USA.
authors.forename: Patsy A
authors.initials: PA
authors.lastname: Willard
authors.affiliation: Pathology and Physiology Research Branch, National Institute for Occupational Safety and Health, Morgantown, WV, USA.
authors.forename: Shannon L
authors.initials: SL
authors.lastname: Case
authors.affiliation: Pathology and Physiology Research Branch, National Institute for Occupational Safety and Health, Morgantown, WV, USA.
authors.forename: Janet A
authors.initials: JA
authors.lastname: Thompson
authors.affiliation: Department of Pharmaceutical Sciences, West Virginia University, Morgantown, WV, USA; Pathology and Physiology Research Branch, National Institute for Occupational Safety and Health, Morgantown, WV, USA.
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Fedan
mesh_terms: D001980:Bronchi / Q000187:drug effects*; D002079:Butter; D002478:Cells, Cultured; D003931:Diacetyl / Q000009:adverse effects*; D004847:Epithelial Cells / Q000187:drug effects*; D005421:Flavoring Agents / Q000009:adverse effects*; D006801:Humans; D019570:Inhalation Exposure / Q000009:adverse effects; D017136:Ion Transport / Q000187:drug effects*; D016210:Methacholine Chloride / Q000009:adverse effects; D008872:Microwaves; D016273:Occupational Exposure / Q000009:adverse effects; D010422:Pentanones / Q000009:adverse effects*
chemical_list: D005421:Flavoring Agents; D010422:Pentanones; D016210:Methacholine Chloride; D002079:Butter; D003931:Diacetyl; C013186:2,3-pentanedione
keywords: 2,3-Pentanedione; Diacetyl; Dicarbonyl/l-xylulose reductase; Human airway epithelial cells; Ion transport; Vapor exposure