Development of a Microscale Cell Culture Analog To Probe Naphthalene Toxicity
Top Cited Papers
- 5 September 2008
- journal article
- research article
- Published by Wiley in Biotechnology Progress
- Vol. 20 (1), 316-323
- https://doi.org/10.1021/bp0341996
Abstract
Prediction of human response to drugs or chemicals is difficult as a result of the complexity of living organisms. We describe an in vitro model that can realistically and inexpensively study the adsorption, distribution, metabolism, elimination, and potential toxicity (ADMET) of chemicals. A microscale cell culture analog (microCCA) is a physical replica of the physiologically based pharmacokinetics (PBPK) model. Such a microfabricated device consists of a fluidic network of channels to mimic the circulatory system and chambers containing cultured mammalian cells representing key functions of animal "organ" systems. This paper describes the application of a two-cell system, four-chamber microCCA ("lung"-"liver"-"other tissue"-"fat") device for proof-of-concept study using naphthalene as a model toxicant. Naphthalene is converted into reactive metabolites (i.e., 1,2-naphthalenediol and 1,2-naphthoquinone) in the "liver" compartment, which then circulate to the "lung" depleting glutathione (GSH) in lung cells. Such microfabricated in vitro devices are potential human surrogates for testing chemicals and pharmaceutics for toxicity and efficacy.Keywords
This publication has 28 references indexed in Scilit:
- Combining Cell Culture Analogue Reactor Designs and PBPK Models to Probe Mechanisms of Naphthalene ToxicityBiotechnology Progress, 2000
- A Fluorescent Cell-Based Assay for Cytochrome P-450 Isozyme 1A2 Induction and InhibitionSLAS Discovery, 2000
- Role of Quinones in ToxicologyChemical Research in Toxicology, 2000
- Age-associated decline in γ-glutamylcysteine synthetase gene expression in ratsFree Radical Biology & Medicine, 2000
- Use of In Vitro Data for Construction of a Physiologically Based Pharmacokinetic Model for Naphthalene in Rats and Mice To Probe Species DifferencesBiotechnology Progress, 1999
- Evidence of Quinone Metabolites of Naphthalene Covalently Bound to Sulfur Nucleophiles of Proteins of Murine Clara Cells after Exposure to NaphthaleneChemical Research in Toxicology, 1997
- Characterisation of the toxic metabolite(s) of naphthaleneToxicology, 1996
- Cytotoxicity and mutagenicity of polycyclic aromatic hydrocarbon o-quinones produced by dihydrodiol dehydrogenaseChemico-Biological Interactions, 1996
- Polycyclic aromatic hydrocarbon (PAH) ortho-quinone conjugate chemistry: Kinetics of thiol addition to PAH ortho-quinones and structures of thioether adducts of naphthalene-1,2-dioneChemico-Biological Interactions, 1992
- Glutathione depletion and cytotoxicity by naphthalene 1,2-oxide in isolated hepatocytesChemico-Biological Interactions, 1989