Toxic effects following phosgene exposure of human epithelial lung cells in vitro using a CULTEX® system

Wijte, Dorien; Alblas, M.J.; Noort, Daan; Langenberg, J.P.; Helden, H.P.M. van

doi:10.1016/j.tiv.2011.09.003

Cited by 16 publications

(9 citation statements)

References 20 publications

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“…The exposure of bacterial and mammalian cells at the air–agar or air–liquid interface to various test atmospheres such as WS and its gas vapour phase, biological and individual chemical pollutants has previously been described elsewhere [Aufderheide and Gressman, 2007; Pariselli et al, ; Schmalz et al, ; Wijte et al, ; Persoz et al, ; Anderson et al, ]. These studies have largely been based around the use of either the CULTEX ® or Vitrocell ® exposure modules.…”

Section: Discussionmentioning

confidence: 99%

Application of a modified gaseous exposure system to the in vitro toxicological assessment of tobacco smoke toxicants

Breheny

Cunningham

Kilford

et al. 2014

Environ and Mol Mutagen

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Tobacco smoke is a complex mixture of over 6,000 individual chemical constituents. Approximately 150 of these have been identified as 'tobacco smoke toxicants' due to their known toxicological effects. A number of these toxicants are present in the gaseous phase of tobacco smoke. This presents a technical challenge when assessing the toxicological effects of these chemicals in vitro. We have adapted a commercially available tobacco smoke exposure system to enable the assessment of the contribution of individual smoke toxicants to the overall toxicological effects of whole mainstream cigarette smoke (WS). Here we present a description of the exposure system and the methodology used. We use the example of a gaseous tobacco smoke toxicant, ethylene oxide (EtO), a Group 1 IARC carcinogen and known mutagen, to illustrate how this methodology can be applied to the assessment of genotoxicity of gaseous chemicals in the context of WS. In the present study we found that EtO was positive in Salmonella typhimurium strain YG1042, a strain that is sensitive to tobacco smoke. However, EtO did not increase the mutagenicity of the WS mixture when it was added at greatly higher concentrations than those found typically in WS. The findings presented here demonstrate the suitability of this exposure system for the assessment of the mutagenic potential of gases in vitro. Whilst we have focused on tobacco smoke toxicants, this system has broad application potential in studying the biological effects of exposure to a wide range of gaseous compounds that are present within complex aerosol mixtures. Environ. Mol. Mutagen. 55:662-672,

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Section: Discussionmentioning

confidence: 99%

Application of a modified gaseous exposure system to the in vitro toxicological assessment of tobacco smoke toxicants

Breheny

Cunningham

Kilford

et al. 2014

Environ and Mol Mutagen

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“…The in vitro setup consists of two Vitrocell ALI modules (one control and one test module) (Vitrocell Systems, Waldkirch, Germany). The ALI exposure system was used as described previously by Wijte and co-workers [7]. The cell cultures of alveolar epithelial cells (A549) and keratinocyte cells (HaCaT) used for the acute toxicity studies are also described [6].…”

Section: Equipmentmentioning

confidence: 99%

“…Various biomarkers reflecting the condition of the cells were measured either in the exposed cells or in the medium after excretion by the cells [7].…”

Section: Introductionmentioning

confidence: 99%

Acute Toxicity Resulting from Human Exposures to Military Smokes

Hulst¹,

Langenberg²,

Klerk³

et al. 2016

Propellants Explo Pyrotec

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The toxicity of smoke‐generating ammunition can be established by looking at the complete hand grenade or only at the smoke composition. In this paper both approaches are described. The toxicity of a signalling smoke was assessed as a complete smoke hand grenade whereas for a 76 mm screening smoke canister only a red phosphorus (RP) pellet was studied. For both smokes the particle size distribution and the toxic effect of the smoke on A549 lung cells in culture in an Air‐Liquid Interface (ALI) system were determined. The assessment of the complete smoke hand grenades also included the determination of the mutagenicity using an Ames test. RP pellets are destined to be burnt on the surface and for this reason the influence of small sand particles on the acute toxicity was also investigated. For both types of smoke the majority of the formed particles were smaller than 2.1 μm, which means that they are capable to penetrate deep into the airways after inhalation. The complete hand grenade approach showed that smoke grenade design can have influence on the final toxicity and mutagenicity of the formed smoke. Sand upon which an RP pellet is burnt can function as a carrier material resulting in an indirect exposure.

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“…Previous in vitro studies on the mechanism of CG toxicity have shown that CG causes an increase in IL-8 as well as a reduction in cell viability and metabolic activity in the immortalized human bronchial epithelial cells 16HBEs (Olivera and Sciuto 2009), small airway cells (Cowan, Smith et al 2004), and in the lung epithelial carcinoma cell line A549 (Wijte, Alblas et al 2011). Moreover, sublethal doses of CG was reported to cause a substantial increase in intracellular free calcium in sheep pulmonary endothelial cells (Werrlein, Kirby et al 1999).…”

Section: Resultsmentioning

confidence: 99%

Transient receptor potential (TRP) channels as a therapeutic target for intervention of respiratory effects and lethality from phosgene

et al. 2016

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Phosgene (CG), a toxic inhalation and industrial hazard, causes bronchoconstriction, vasoconstriction and associated pathological effects that could be life threatening. Ion channels of the transient receptor potential (TRP) family have been identified to act as specific chemosensory molecules in the respiratory tract in the detection, control of adaptive responses and initiation of detrimental signaling cascades upon exposure to various toxic inhalation hazards (TIH); their activation due to TIH exposure may result in broncho- and vasoconstriction. We studied changes in the regulation of intracellular free Ca2+ concentration ([Ca2+]i) in cultures of human bronchial smooth muscle cells (BSMC) and human pulmonary microvascular endothelial cells (HPMEC) exposed to CG (16 ppm, 8 min), using an air/liquid interface exposure system. CG increased [Ca2+]i (p<0.05) in both cell types, The CG-induced [Ca2+]i was blocked (p<0.05) by two types of TRP channel blockers, SKF-96365, a general TRP channel blocker, and RR, a general TRPV (vanilloid type) blocker, in both BSMC and HPMEC. These effects correlate with the in vivo efficacies of these compounds to protect against lung injury and 24 hr lethality from whole body CG inhalation exposure in mice (8-10 ppm × 20 min). Thus the TRP channel mechanism appears to be a potential target for intervention in CG toxicity.

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Toxic effects following phosgene exposure of human epithelial lung cells in vitro using a CULTEX® system

Cited by 16 publications

References 20 publications

Application of a modified gaseous exposure system to the in vitro toxicological assessment of tobacco smoke toxicants

Application of a modified gaseous exposure system to the in vitro toxicological assessment of tobacco smoke toxicants

Acute Toxicity Resulting from Human Exposures to Military Smokes

Transient receptor potential (TRP) channels as a therapeutic target for intervention of respiratory effects and lethality from phosgene

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