| 1976079 |
Forkert PG, Geddes BA, Birch DW, Massey TE: 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. Drug Metab Dispos. 1990 Jul-Aug;18(4):534-9.
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. |
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