Cytotoxicity of NO2 gas to cultured human and murine cells in an inverted monolayer exposure system

Tu, Ba; Wallin, Alf; Moldéus, Peter; Cotgreave, Ian A.

doi:10.1016/0300-483x(94)02909-e

Cited by 28 publications

(11 citation statements)

References 33 publications

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“…2B) and are then transformed to sulfuric and nitric acids, respectively, resulting in that the acidic environment likely causes direct damage to membrane proteins of A549 cells. This process is assumed to sufficiently take place at a lower concentration range of SO2 and NO2 gases, since it has previously been reported that the concentration of intercellular glutathione decreases upon exposure to 1 -20ppm NO2 gas for 1 h. 27 Note that glutathione is an important antioxidant in maintaining the intracellular redox balance to protect against oxidants, free radicals, and electrophiles. [28][29][30] In contrast, since CO does not produce acids in the aqueous media (Fig.…”

Section: Responses Of Cells To Gaseous Compoundsmentioning

confidence: 99%

Development of an in vitro Batch-type Closed Gas Exposure Device with an Alveolar Epithelial Cell Line, A549, for Toxicity Evaluations of Gaseous Compounds

et al. 2008

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To simply evaluate toxicity for various types of exhaust-gas samples collected in various locations, we developed a smallscale (150 mL) batch-type completely closed gas exposure device incorporated with an air-liquid interface culture of a human alveolar epithelial cell line, A549. On the basis of cell viability tests using an acid phosphatase assay after 48 h of gas exposure, the developed device was able to measure clear dose-response relationships for volatile organic and inorganic compounds, such as benzene, trichloroethylene (TCE), acetone, SO2 and NO2 gases, but not CO gas. Although the 50% effective concentration values in the device were much higher than 50% lethal concentration values reported in animal experiments, the tendency of the toxic intensity observed in the former was roughly consistent with that of the acute toxicity in the latter. We further applied the device to evaluate the toxicity of cigarette smoke as an example of actual environmental gases, and successfully measured acute cell death from the gas after 48 h of exposure. The present small device is expected to be one of good tools not only in simultaneously assessing various gaseous chemicals or samples, but also in studying acute toxicity expression mechanisms in human lung epithelia.

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Section: Responses Of Cells To Gaseous Compoundsmentioning

confidence: 99%

Development of an in vitro Batch-type Closed Gas Exposure Device with an Alveolar Epithelial Cell Line, A549, for Toxicity Evaluations of Gaseous Compounds

et al. 2008

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“…The majority of in vitro studies for assessing the health effects relating to smoke toxicity have been derived from studies of carbon monoxide (Lee II et al, 1981), nitrogen dioxide (Tu et al, 1995;Aufderheide et al, 2002), volatile organic compounds (Bonsi et al, 2002), combustion particles (Okeson et al, 2003), and smoke toxicity derived from cigarettes and diesel exhausts Ritter et al, 2003;Ritter et al, 2004). However, to our knowledge no in vitro test system is currently accepted or validated for the study of toxic effects derived from fire combustion products using human cells.…”

Section: Introductionmentioning

confidence: 99%

“…The system must be practical, reliable and suitable to ensure the effective contact between combustion toxicants and cells whilst closely simulating human exposure conditions. In the area of in vitro toxicity studies for inhalation, sampling and exposure methods have been investigated using the following four techniques: (a) sampling the particulate phase on filters followed by the investigation of the effects of suspended or extracted particles (Bay et al, 2001;Putnam et al, 2002;Tewes et al, 2003;Roemer et al, 2004) (b) sampling the gas phase in a culture medium, PBS (phosphate buffer solution) (Tewes et al, 2003;Roemer et al, 2004) and DMSO (dimethyl sulfoxide) (c) exposure of adherent or suspended cells covered by medium to the gas phase (Lee II et al, 1981;Tu et al, 1995) and (d) direct exposure at the air/liquid interface with a specific flow rate Ritter et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

Comparative assessment of threein vitro exposure methods for combustion toxicity

et al. 2006

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A comparative assessment of three approaches for the use of human cells in vitro to investigate combustion toxicity was conducted. These included one indirect and two direct (passive and dynamic) exposure methods. The indirect method used an impinger system in which culture medium was used to trap the toxicants, whilst the direct exposure involved the use of a Horizontal Harvard Navicyte Chamber at the air/liquid interface. The cytotoxic effects of thermal decomposition products were assessed using the MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) assay (Promega) on a selection of human cells including: HepG2, A549 and skin fibroblasts. A small scale laboratory fire test using a vertical tube furnace was designed for the generation of combustion products. Polymethyl methacrylate (PMMA) was selected as a model polymer to study the cytotoxic effects of combustion products. NOAEC (no observable adverse effect concentration), IC10 (10% inhibitory concentration), IC50 (50% inhibitory concentration) and TLC (total lethal concentration) values were determined from dose response curves. Assessment using the NRU (neutral red uptake) and ATP (adenosine triphosphate) assays on human lung derived cells (A549) was also undertaken. Comparison between in vitro cytotoxicity results against published toxicity data for PMMA combustion and predicted LC50 (50% lethal concentration) values calculated from identified compounds using GCMS (gas chromatography mass spectrometry) was determined. The results suggested that the indirect exposure method did not appear to simulate closely exposure via inhalation, whilst exposure at the air/liquid interface by using the dynamic method proved to be a more representative method of human inhalation. This exposure method may be a potential system for in vitro cytotoxicity testing in combustion toxicity.

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“…A human pulmonary type II-like epithelial cell line A-549 has been found to acquire considerable resistance to exogenous NO 2 , perhaps due to considerably higher levels of cellular glutathione [6]. On the contrary, HUVEC and C-21 cell lines display both low pre-exposure GSH (reduced glutathione) levels and a high sensitivity to NO 2 [6].…”

Section: Introductionmentioning

confidence: 99%

“…On the contrary, HUVEC and C-21 cell lines display both low pre-exposure GSH (reduced glutathione) levels and a high sensitivity to NO 2 [6]. However, the reasons for intracellular variation in NO 2 sensitivity remain poorly understood.…”

Section: Introductionmentioning

confidence: 99%

A Novel Biosensor for Evaluation of Apoptotic or Necrotic Effects of Nitrogen Dioxide during Acute Pancreatitis in Rat

Jacewicz

Dąbrowska

Wyrzykowski

et al. 2009

Sensors

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The direct and accurate estimation of nitric dioxide levels is an extremely laborious and technically demanding procedure in the molecular diagnostics of inflammatory processes. The aim of this work is to demonstrate that a stop-flow technique utilizing a specific spectroscopic biosensor can be used for detection of nanomolar quantities of NO2 in biological milieu. The use of novel compound cis-[Cr(C2O4)(AaraNH2)(OH2)2]+ increases NO2 estimation accuracy by slowing down the rate of NO2 uptake. In this study, an animal model of pancreatitis, where nitrosative stress is induced by either 3g/kg bw or 1.5 g/kg bw dose of l-arginine, was used. Biochemical parameters and morphological characteristics of acute pancreatitis were monitored, specifically assessing pancreatic acinar cell death mode, NO2 generation and cellular glutathione level. The severity of the process correlated positively with NO2 levels in pancreatic acinar cell cytosol samples, and negatively with cellular glutathione levels.

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Cytotoxicity of NO2 gas to cultured human and murine cells in an inverted monolayer exposure system

Cited by 28 publications

References 33 publications

Development of an in vitro Batch-type Closed Gas Exposure Device with an Alveolar Epithelial Cell Line, A549, for Toxicity Evaluations of Gaseous Compounds

Development of an in vitro Batch-type Closed Gas Exposure Device with an Alveolar Epithelial Cell Line, A549, for Toxicity Evaluations of Gaseous Compounds

Comparative assessment of threein vitro exposure methods for combustion toxicity

A Novel Biosensor for Evaluation of Apoptotic or Necrotic Effects of Nitrogen Dioxide during Acute Pancreatitis in Rat

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