In vitro tests of neurotoxicity

Abdulla, Elizabeth McFarlane; Campbell, Iain C.

doi:10.1016/1056-8719(93)90053-h

Cited by 18 publications

(9 citation statements)

References 21 publications

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“…Epithelial cells cultured from various tissues have served as models for studies on mechanisms of growth regulation, differentiation, tumorigenesis, and infection, and for testing the cytotoxicity/genotoxicity of drugs and other chemicals [4][5][6][7][8][9]. Keratinocytes cultured from different mucosal compartments are not equivalent in terms of susceptibility to toxic agents and pathogens of sexually transmitted diseases (STDs) [8,10,11].…”

Section: Introductionmentioning

confidence: 99%

Generation of Papillomavirus-Immortalized Cell Lines from Normal Human Ectocervical, Endocervical, and Vaginal Epithelium that Maintain Expression of Tissue-Specific Differentiation Proteins1

Fichorova¹,

Rheinwald²,

Anderson³

1997

Biology of Reproduction

281

284

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We have established and characterized three cell lines from normal human vaginal, ectocervical, and endocervical epithelia immortalized by expression of human papillomavirus 16/E6E7. The lines (VK2/E6E7, Ect1/E6E7, and End1/E6E7) displayed distinctive morphologies at the level of light microscopy when cultured in calcium-supplemented (0.4 mM) keratinocyte serum-free medium and maintained a stable phenotype after more than 1 yr of continuous passage. They were compared to primary cell cultures and epithelial cells in sections of the respective native tissues for expression of epithelial differentiation proteins. All cell lines expressed cytokeratin (CK) 8, CK18, and CK19, and some cells in all three cell lines expressed CK16, involucrin, and the secretory component of the polymeric immunoglobulin receptor. The vaginal and ectocervical cell lines expressed CK10 and CK13, whereas the endocervical line did not. With the exception of CK8 and CK18 expression, the morphological and immunocytochemical characteristics of the immortalized lines closely resembled those of their respective tissues of origin and primary cultures, and all differed significantly from the HeLa cervical adenocarcinoma cell line. These new cell lines may provide the basis for valid, reproducible in vitro models for studies on cervicovaginal physiology and infections and for testing pharmacological agents for intravaginal application.

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Section: Introductionmentioning

confidence: 99%

Generation of Papillomavirus-Immortalized Cell Lines from Normal Human Ectocervical, Endocervical, and Vaginal Epithelium that Maintain Expression of Tissue-Specific Differentiation Proteins1

Fichorova¹,

Rheinwald²,

Anderson³

1997

Biology of Reproduction

281

284

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“…Redox modulation of the ASIC current in acutely dissociated mouse cortical neurons Prenatal cell cultures likely contain various immature neurons (Lendahl and McKay, 1990;Abdulla and Campbell, 1993). The properties of ion channels expressed in these neurons, and their modulation by redox reagents, may not be comparable with those expressed in mature and fully differentiated neurons.…”

Section: Modulation Of Asic Current By Reducing Agents Requires Chemimentioning

confidence: 99%

ASIC1a-Specific Modulation of Acid-Sensing Ion Channels in Mouse Cortical Neurons by Redox Reagents

Chu¹,

Close²,

Saugstad³

et al. 2006

J. Neurosci.

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Acid-sensing ion channel (ASIC)-1a, the major ASIC subunit with Ca 2ϩ permeability, is highly expressed in the neurons of CNS. Activation of these channels with resultant intracellular Ca 2ϩ accumulation plays a critical role in normal synaptic plasticity, learning/memory, and in acidosis-mediated glutamate receptor-independent neuronal injury. Here we demonstrate that the activities of ASICs in CNS neurons are tightly regulated by the redox state of the channels and that the modulation is ASIC1a subunit dependent. In cultured mouse cortical neurons, application of the reducing agents dramatically potentiated, whereas the oxidizing agents inhibited the ASIC currents. However, in neurons from the ASIC1 knock-out mice, neither oxidizing agents nor reducing reagents had any effect on the acid-activated current. In Chinese Hamster Ovary cells, redox-modifying agents only affected the current mediated by homomeric ASIC1a, but not homomeric ASIC1b, ASIC2a, or ASIC3. In current-clamp recordings and Ca 2ϩ -imaging experiments, the reducing agents increased but the oxidizing agents decreased acid-induced membrane depolarization and the intracellular Ca 2ϩ accumulation. Site-directed mutagenesis studies identified involvement of cysteine 61 and lysine 133, located in the extracellular domain of the ASIC1a subunit, in the modulation of ASICs by oxidizing and reducing agents, respectively. Our results suggest that redox state of the ASIC1a subunit is an important factor in determining the overall physiological function and the pathological role of ASICs in the CNS.

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“…Several in vitro systems can be considered as alternative testing systems for Environmental Health Perspectives * Vol 106, Supplement 2 * April 1998 neurotoxicity (19)(20)(21)(22). In decreasing order of complexity these models include organotypic explants, brain slices, reaggregate cultures, primary cell preparations, and established cell lines.…”

Section: Current Methods For Organotypic Culturesmentioning

confidence: 99%

13th Meeting of the Scientific Group on Methodologies for the Safety Evaluation of Chemicals (SGOMSEC): alternative testing methodologies for organ toxicity.

Spielmann

Bochkov

Costa

et al. 1998

Environ Health Perspect

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In the past decade in vitro tests have been developed that represent a range of anatomic structure from perfused whole organs to subcellular fractions. To assess the use of in vitro tests for toxicity testing, we describe and evaluate the current status of organotypic cultures for the major target organs of toxic agents. This includes liver, kidney, neural tissue, the hematopoietic system, the immune system, reproductive organs, and the endocrine system. The second part of this report reviews the application of in vitro culture systems to organ specific toxicity and evaluates the application of these systems both in industry for safety assessment and in government for regulatory purposes. Members of the working group (VWG) felt that access to high-quality human material is essential for better use of in vitro organ and tissue cultures in the risk assessment process. Therefore, research should focus on improving culture techniques that will allow better preservation of human material. The WG felt that it is also important to develop and make available relevant reference compounds for toxicity assessment in each organ system, to organize and make available via the Internet complete in vivo toxicity data, including human data, containing dose, end points, and toxicokinetics. The WG also recommended that research should be supported to identify and to validate biological end points for target organ toxicity to be used in alternative toxicity testing strategies.

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In vitro tests of neurotoxicity

Cited by 18 publications

References 21 publications

Generation of Papillomavirus-Immortalized Cell Lines from Normal Human Ectocervical, Endocervical, and Vaginal Epithelium that Maintain Expression of Tissue-Specific Differentiation Proteins1

Generation of Papillomavirus-Immortalized Cell Lines from Normal Human Ectocervical, Endocervical, and Vaginal Epithelium that Maintain Expression of Tissue-Specific Differentiation Proteins1

ASIC1a-Specific Modulation of Acid-Sensing Ion Channels in Mouse Cortical Neurons by Redox Reagents

13th Meeting of the Scientific Group on Methodologies for the Safety Evaluation of Chemicals (SGOMSEC): alternative testing methodologies for organ toxicity.

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