An improved in vitro model for testing the pulmonary toxicity of complex mixtures such as cigarette smoke

Aufderheide, Michaela; Knebel, Jan; Ritter, Detlef

doi:10.1078/0940-2993-00298

Cited by 68 publications

(31 citation statements)

References 11 publications

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“…Initially, tobacco smoke studies utilized the particulate fraction of cigarette smoke, and not the complete aerosol. More than 6,000 chemicals have been identified in tobacco smoke aerosol, and recent emphasis on direct exposure to the full content of primary and SHS (1,22,24,34) presents a more realistic approach for comparison to human tobacco use (41). To translate applicable effects of involuntary smoke exposure, we utilized a nose-only exposure system calibrated to deliver controlled doses of SHS (InExpose System, Scireq).…”

mentioning

confidence: 99%

Acute secondhand smoke-induced pulmonary inflammation is diminished in RAGE knockout mice

Wood

Winden

Marlor

et al. 2014

American Journal of Physiology-Lung Cellular and Molecular Phys

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The receptor for advanced glycation end-products (RAGE) has increasingly been demonstrated to be an important modulator of inflammation in cases of pulmonary disease. Published reports involving tobacco smoke exposure have demonstrated increased expression of RAGE, its participation in proinflammatory signaling, and its role in irreversible pulmonary remodeling. The current research evaluated the in vivo effects of short-term secondhand smoke (SHS) exposure in RAGE knockout and control mice compared with identical animals exposed to room air only. Quantitative PCR, immunoblotting, and immunohistochemistry revealed elevated RAGE expression in controls after 4 wk of SHS exposure and an anticipated absence of RAGE expression in RAGE knockout mice regardless of smoke exposure. Ras activation, NF-κB activity, and cytokine elaboration were assessed to characterize the molecular basis of SHS-induced inflammation in the mouse lung. Furthermore, bronchoalveolar lavage fluid was procured from RAGE knockout and control animals for the assessment of inflammatory cells and molecules. As a general theme, inflammation coincident with leukocyte recruitment was induced by SHS exposure and significantly influenced by the availability of RAGE. These data reveal captivating information suggesting a role for RAGE signaling in lungs exposed to SHS. However, ongoing research is still warranted to fully explain roles for RAGE and other receptors in cells coping with involuntary smoke exposure for prolonged periods of time.

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mentioning

confidence: 99%

Acute secondhand smoke-induced pulmonary inflammation is diminished in RAGE knockout mice

Wood

Winden

Marlor

et al. 2014

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…After discussions with, and supported by, scientists from the cigarette industry the scope of investigations was now expanded to include cigarette mainstream smoke. First results of assessing the behavior and (toxicological) effects of native, physically unmodified cigarette mainstream smoke under ALI conditions, employing the Cultex ® system, were reported in 2003 by RITTER et al (444) and AUFDERHEIDE et al (445); "unmodified" relating to the fact that the smoke was neither heated or humidified nor enriched with carbon dioxide -manipulations with strong potential influence on particle quality and number. The studies used the 1R4F Kentucky reference cigarette and two experimental cigarettes with different ISO "tar" levels (9.0 mg and 1.4 mg).…”

Section: Air-liquid Interface (Ali) Exposure Systems: Cultex ®mentioning

confidence: 99%

“…In contrast, glutathione was down to 10% after exposure but had shot up to about 175% after recovery -an "overshoot" reaction typical for intensified cellular defense response. The authors (444,445) underlined that the in vitro exposure system using ALI technology minimized smoke transformation due to physical and chemical changes during generation and exposure. Intermittent smoke exposure with intermediate availability of fresh air was coming quite close to the physiological situation.…”

Section: Air-liquid Interface (Ali) Exposure Systems: Cultex ®mentioning

confidence: 99%

“…Intermittent smoke exposure with intermediate availability of fresh air was coming quite close to the physiological situation. Using the same equipment -as in the two studies (444,445) just discussed -for smoke generation and dilution, online monitoring and the exposure of cells at the ALI, RITTER et al (446) took a functional approach to the comparative in vitro testing of cigarette mainstream smoke toxicity. The test battery included the 1R4F Kentucky reference cigarette (9.2 mg "tar") and two commercial light filter brands from Italy and Greece with identical (imprinted) "tar" yields of 7.0 mg.…”

Section: Air-liquid Interface (Ali) Exposure Systems: Cultex ®mentioning

confidence: 99%

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Cigarette Mainstream Smoke: The Evolution of Methods and Devices for Generation, Exposure and Collection

Klus¹,

Boenke-Nimphius²,

Müller

2016

Beiträge Zur Tabakforschung International/Contributions to Tobacco Research

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SUMMARYThe objective of this review is to support tobacco scientists when evaluating information published on smoking machines, and on cigarette mainstream smoke (in vivo and in vitro) exposure systems and collection devices. The intriguing development of smoking machines (mainly for cigarettes) is followed for more than 170 years -from the first simple set-ups in the 1840s to the sophisticated and fully automated analytical smoking machines available today. Systems for the large-scale production of smoke (condensate) for preparative work are equally considered. The standardization of machine smoking methods and test pieces has solved several technical problems and produced sensible rules but, at the same time, given rise to new controversies like the compatibility of artificial and human smoking, and the implementation of more intense machine smoking regimes. Adequate space is allotted for the discussion of configurations for in vivo smoke exposure of rodent and non-rodent species and the machines generating the required smoke (condensate). Covered as well is the field of in vitro toxicity testing, including the increasingly informative new techniques of air-liquid interface exposure, which are becoming more and more refined with the use of organotypic cultures and genetic analyses. The review is completed by the examination of the considerable variety of mainstream smoke collection devices (filters and traps) developed over time -some for very specific purposes -and refers to the perpetual problem of artifact formation by aging.

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“…3 Various ALIC-based evaluation systems for gaseous toxicities have previously been reported by several researchers. [5][6][7][8][9][10][11][12] Some of the devices have been applied to evaluate the toxicities for actual environmental gases, such as cigarette smoke, 8,9 diesel exhaust emission, 10 and combustion gas. 11 However, since most devices reported previously are large scale and continuous flow-based systems, several handled liters of sample gases are necessary.…”

Section: Introductionmentioning

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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An improved in vitro model for testing the pulmonary toxicity of complex mixtures such as cigarette smoke

Cited by 68 publications

References 11 publications

Acute secondhand smoke-induced pulmonary inflammation is diminished in RAGE knockout mice

Acute secondhand smoke-induced pulmonary inflammation is diminished in RAGE knockout mice

Cigarette Mainstream Smoke: The Evolution of Methods and Devices for Generation, Exposure and Collection

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

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