Document Detail

Morphologic changes and covalent binding of 1,1-dichloroethylene in Clara and alveolar type II cells isolated from lungs of mice following in vivo administration.
MedLine Citation:
PMID:  1976079     Owner:  NLM     Status:  MEDLINE    
We have investigated the metabolism and covalent binding of 1,1-dichloroethylene (1,1-DCE) in isolated unseparated lung cells and in enriched fractions of Clara and alveolar type II cells from mice. Lung cells from control mice separated by centrifugal elutriation were viable and metabolically active as assessed by measurements of 7-ethoxycoumarin deethylase, NADPH cytochrome c reductase, and glutathione S-transferase activities, which were highest in fractions enriched in Clara cells. Mice were treated with [14C]1,1-DCE (125 mg/kg; 20 microCi/kg) in vivo and, 1 hr later, lung cells were isolated and binding of [14C]1,1-DCE determined. Covalent binding was highest in the Clara cell fraction (480 +/- 205 pmol/10(6) cells; 41% Clara cell purity) when compared to the levels present in the fractions containing type II cells (126 +/- 63 pmol/10(6) cells; 51% type II cell purity) and mixed cells from whole lung (29 +/- 13 pmol/10(6) cells). Ultrastructurally, alveolar type II cells from lungs of control and 1,1-DCE-treated mice exhibited normal morphology with well-preserved lamellar bodies. Whereas Clara cells isolated from lungs of control mice appeared structurally unimpaired, those from the lungs of 1,1-DCE-treated mice displayed severe damage and disruption of cellular organelles. The results of these experiments demonstrate the highest binding of [14C]1,1-DCE-metabolite(s) in Clara cells, whereas significantly lower binding was found in both alveolar type II and unseparated lung cells. The substantial binding of [14C]1,1-DCE in Clara cells correlated positively with the high monooxygenase capacity and the preferential damage sustained by this cell population.
P G Forkert; B A Geddes; D W Birch; T E Massey
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Drug metabolism and disposition: the biological fate of chemicals     Volume:  18     ISSN:  0090-9556     ISO Abbreviation:  Drug Metab. Dispos.     Publication Date:    1990 Jul-Aug
Date Detail:
Created Date:  1990-10-19     Completed Date:  1990-10-19     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9421550     Medline TA:  Drug Metab Dispos     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  534-9     Citation Subset:  IM    
Department of Anatomy, Queen's University, Kingston, Ontario, Canada.
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MeSH Terms
Ethylene Dichlorides / metabolism*
Hydrocarbons, Chlorinated / metabolism*
Lung / cytology,  enzymology,  metabolism*
Microscopy, Electron
Pulmonary Alveoli / enzymology,  metabolism,  ultrastructure
Reg. No./Substance:
0/Ethylene Dichlorides; 0/Hydrocarbons, Chlorinated; 107-06-2/ethylene dichloride

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