Document Detail

The use of an in vitro submerged keratinocyte model to predict induction of squamous metaplasia.
MedLine Citation:
PMID:  11566574     Owner:  NLM     Status:  MEDLINE    
An in vitro submerged keratinocyte model of squamous metaplasia (SQ) in epithelia is being developed to assess the risk associated with exposure to certain environmental agents. Tracheobronchial epithelium (TBE) in vivo can respond to airborne environmental insult by becoming squamous. Epidemiological evidence suggests that cigarette smoke is capable of inducing this change. Retinoic acid has been shown to maintain cells in the mucociliary state. SQ is considered protective and adaptive but potentially preneoplastic if unrelenting and is used histologically in the diagnosis of squamous cell carcinoma. SQ is characterised by upregulation of the expression of transglutaminase I (TGI), TGI activity leading to the formation of isopeptide cross-linked envelopes and replacement of the mucociliary cell type with non-polar squamous cells out of contact with the basal lamina. The ability of the in vitro keratinocyte submerged model to predict the squamous metaplastic response in vivo has been investigated in vitro using TG catalysed fluorescein cadaverine incorporation as a measure of cross-linked envelope formation, Alamar blue conversion to measure viability and Coomassie blue incorporation to measure total cellular protein. The modulation of the squamous condition by retinoic acid (RA), cigarette smoke condensate (CSC) and nicotine has been assessed in keratinocytes cultured in Green's medium. RA inhibited FC incorporation by 95% at 1 x 10(-5) M and simultaneously increased cell viability providing evidence to support its role in the regulation of the non-differentiated state. Nicotine (0-1 mg/ml) induced a dose-dependent increase in viability at 6 days, a response that was accompanied by an increase in FC incorporation at 12 days. CSC (0-5 microg/ml) increased FC incorporation after 12 days. Hence, nicotine modulated the squamous condition by up-regulating TGI activity following a period of hyperactivity. CSC induced a gradual change to the differentiated state and RA served to maintain the cells in an undifferentiated state.
A C Gray; R H Clothier
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Toxicology in vitro : an international journal published in association with BIBRA     Volume:  15     ISSN:  0887-2333     ISO Abbreviation:  Toxicol In Vitro     Publication Date:    2001 Aug-Oct
Date Detail:
Created Date:  2001-09-21     Completed Date:  2001-12-04     Revised Date:  2009-04-10    
Medline Journal Info:
Nlm Unique ID:  8712158     Medline TA:  Toxicol In Vitro     Country:  England    
Other Details:
Languages:  eng     Pagination:  427-31     Citation Subset:  IM    
FRAME Alternatives Laboratory, School of Biomedical Sciences, Medical School, University of Nottingham, Nottingham NG7 2UH, UK.
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MeSH Terms
Animal Testing Alternatives
Cadaverine / metabolism
Cell Differentiation / drug effects
Cell Survival / drug effects
Cells, Cultured
Coloring Agents / metabolism
Cross-Linking Reagents / metabolism
Dose-Response Relationship, Drug
Fluorescein / metabolism
Keratinocytes / drug effects,  enzymology,  pathology*
Metaplasia / etiology
Nicotine / toxicity
Proteins / metabolism
Tars / toxicity
Transglutaminases / metabolism
Tretinoin / toxicity
Reg. No./Substance:
0/Coloring Agents; 0/Cross-Linking Reagents; 0/Oxazines; 0/Proteins; 0/Tars; 0/Xanthenes; 0/tobacco tar; 2321-07-5/Fluorescein; 302-79-4/Tretinoin; 462-94-2/Cadaverine; 54-11-5/Nicotine; 550-82-3/resazurin; EC; EC 1

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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