Characterization of the Vitrocell® 24/48 in vitroaerosol exposure system using mainstream cigarette smoke

Majeed, Shoaib; Frentzel, Stefan; Wagner, Sandra; Kuehn, Diana; Leroy, Patrice; Guy, Philippe A.; Knorr, Arno; Hoeng, Julia; Peitsch, Manuel C.

doi:10.1186/s13065-014-0062-3

Cited by 69 publications

(69 citation statements)

References 26 publications

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“…The experiments were conducted with the VITROCELL ® cultivation and exposure system (12 HT/HT CF modules Waldkirch, Germany) with 6 cell culture inserts which is based on the cultivation of cells on porous membrane (Majeed et al 2014). The system has separate exposure modules, each positioning three inserts which were used for parallel exposures to controls and test compounds.…”

Section: Methodsmentioning

confidence: 99%

“…It mimics the physiological conditions in the respiratory tract and eliminates the interactions of potential constituents with culture media (Thorne and Adamson 2013). These experiments were conducted with the buccal cells (TR-146) and with the human cell line A-459 which is derived from lung fibroblasts (Lieber et al 1976) and was used in earlier gaseous exposure experiments (Majeed et al 2014; Tang et al 2012). …”

Section: Introductionmentioning

confidence: 99%

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Genotoxic properties of XLR-11, a widely consumed synthetic cannabinoid, and of the benzoyl indole RCS-4

et al. 2016

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Aim of this study was the investigation of the genotoxic properties of XLR-11 [1-(5-fluoropentyl)-1H-indol-3-yl](2,2,3,3-tetramethylcyclopropyl)methanone, a widely consumed synthetic cannabinoid (SC), and of the benzoyl indole RCS-4 (4-methoxyphenyl)(1-pentyl-1H-indol-3-yl)methanone). We characterized the DNA-damaging properties of these drugs in different experimental systems. No evidence for induction of gene mutations was detected in bacterial (Salmonella/microsome) tests, but clear dose-dependent effects were found in in vitro single cell gel electrophoresis (SCGE) assays with human lymphocytes and with buccal- and lung-derived human cell lines (TR-146 and A-549). These experiments are based on the determination of DNA migration in an electric field and enable the detection of single- and double-strand breaks and apurinic sites. Furthermore, we found that both drugs induce micronuclei which are formed as a consequence of chromosomal aberrations. The lack of effects in SCGE experiments with lesion-specific enzymes (FPG, Endo III) shows that the DNA damage is not caused by formation of oxidatively damaged bases; experiments with liver enzyme homogenates and bovine serum albumin indicate that the drugs are not converted enzymatically to DNA-reactive intermediates. Furthermore, results with buccal- and lung-derived human cells show that gaseous treatment of the cells under conditions which reflect the exposure situation in drug users may cause damage of the genetic material in epithelia of the respiratory tract. Since DNA instability is involved in the etiology of cancer, these findings can be taken as an indication that consumption of the SCs may cause tumors in the respiratory tract of consumers.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Genotoxic properties of XLR-11, a widely consumed synthetic cannabinoid, and of the benzoyl indole RCS-4

et al. 2016

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“…The smoke/aerosol was trapped in EXtrelut ® 3NT columns soaked with 2 ml of 0.5 M H 2 SO 4 solution, as previously reported (Majeed et al, 2014). Nicotine concentrations were measured using gas chromatography-flame ionization detection.…”

Section: Organotypic Tissue Culture Modelsmentioning

confidence: 99%

“…Briefly, before exposure, each row in the Cultivation Base Module of the Vitrocell ® 24/48 exposure system was filled with 18.5 ml PBS. Following exposure to diluted 3R4F smoke or THS2.2 aerosol, an aliquot of 1.2 ml PBS-exposed sample (per row) was collected and subjected to a high-performance liquid chromatography (HPLC) coupled with a tandem MS (HPLC-MS/MS) analysis, as previously reported (Majeed et al, 2014).…”

Section: Fig 1: Experimental Designmentioning

confidence: 99%

3-D nasal cultures: Systems toxicological assessment of a candidate modified-risk tobacco product

Iskandar

Mathis

Martin

et al. 2017

ALTEX

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ratory animals -to reduce the number of animals, to refine the design of procedures such that pain and distress are minimized, and to replace animal models with alternative methods and lower organisms when possible (Doke and Dhawale, 2015). In this regard, the capability to preserve human respiratory cells in culture provides a tool not only to generate mechanistic data, but also to improve the predicted effects of exposure hazard through inhalation in humans. An emphasis on assessment studies using human-derived in vitro culture systems will reduce the problems that are inherent to interspecies translatability (Manuppello and Sullivan, 2015).In vitro toxicology approaches have evolved from focusing on the molecular changes within a cell to understanding the toxicity-related mechanisms (cell-cell interactions) in models IntroductionMechanistic investigation of the impact of exposure on the lower airway remains challenging because access to lung tissues is limited. Although biopsy samples can be obtained from patients/donors for mechanistic studies of exposure-induced injury, a biopsy procedure is invasive and there are related ethical concerns (Peppercorn, 2013). Alternatively, animal studies allow the collection of biological samples from various animal models of human diseases. However, biological responses can vary among animal species, and findings obtained from animal studies may not apply to humans. Alternatives to animal testing have been proposed to overcome these drawbacks, including the 3Rs strategy -reduction, refinement, and replacement of labo- Research SummaryIn vitro toxicology approaches have evolved from a focus on molecular changes within a cell to understanding of toxicity-related mechanisms in systems that can mimic the in vivo environment. The recent development of three dimensional (3-D) organotypic nasal epithelial culture models offers a physiologically robust system for studying the effects of exposure through inhalation. Exposure to cigarette smoke (CS) is associated with nasal inflammation; thus, the nasal epithelium is relevant for evaluating the pathophysiological impact of CS exposure. The present study investigated further the application of in vitro human 3-D nasal epithelial culture models for toxicological assessment of inhalation exposure. Aligned with 3Rs strategy, this study aimed to explore the relevance of a human 3-D nasal culture model to assess the toxicological impact of aerosols generated from a candidate modified risk tobacco product (cMRTP), the Tobacco Heating System (THS) 2.2, as compared with smoke generated from reference cigarette 3R4F. A series of experimental repetitions, where multiple concentrations of THS2.2 aerosol and 3R4F smoke were applied, were conducted to obtain reproducible measurements to understand the cellular/molecular changes that occur following exposure. In agreement with "Toxicity Testing in the 21 st Century -a Vision and a Strategy", this study implemented a systems toxicology approach and found that for all tested concentrations the impa...

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“…Technically, it represents the straight doubling of the 24-well system (504) and is housed in a climatic chamber. MAJEED et al (506) examined the smoke dilution and exposure capabilities of the Vitrocell ® 24/48 in combination with the fully automated 30-port carousel SM2000 smoking machine (507). This machine was manufactured by Burghart Messtechnik GmbH (Wedel, Germany; the company ceased operations in 2015) according to Philip Morris specifications and became commercially available.…”

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

confidence: 99%

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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Characterization of the Vitrocell® 24/48 in vitroaerosol exposure system using mainstream cigarette smoke

Cited by 69 publications

References 26 publications

Genotoxic properties of XLR-11, a widely consumed synthetic cannabinoid, and of the benzoyl indole RCS-4

Genotoxic properties of XLR-11, a widely consumed synthetic cannabinoid, and of the benzoyl indole RCS-4

3-D nasal cultures: Systems toxicological assessment of a candidate modified-risk tobacco product

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

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