The mechanism of carbon tetrachloride induced pulmonary Clara cell damage: biochemical and morphologic studies.
In our present study, we have shown the different damages among pulmonary drug metabolizing systems and selective lesions of the pulmonary Clara cells in mice treated with carbon tetrachloride. Concerning with the inhibition degrees of pulmonary drug metabolizing systems, the inhibition of coumarin hydroxylase activity was the severest in this experiment. Moreover, at the in vitro carbon tetrachloride exposure study to estimate carbon tetrachloride metabolizing capacity, the severe degradation of coumarin hydroxylase activity was observed, while 7-ethoxycoumarin o-deethylase and NADPH-cytochrome c reductase activities only showed slight degradations by carbon tetrachloride treatment. From these results, it is suggested that cytochrome P-450 form which catalyzes coumarin hydroxylation may highly localize in the Clara cell and have carbon tetrachloride metabolizing activity.
Yano
T
T
Department of Pathology, Yokohama City University School of Medicine, Japan.
Shibagaki
T
T
Kitamura
H
H
Kanisawa
M
M
D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases; D001980:Bronchi / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002251:Carbon Tetrachloride / Q000378:metabolism / Q000633:toxicity*; D065637:Cytochrome P-450 CYP2A6; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D006651:Histocytochemistry; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D006899:Mixed Function Oxygenases / Q000037:antagonists & inhibitors; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000378:metabolism / Q000473:pathology
D003577:Cytochrome P-450 Enzyme System; D002251:Carbon Tetrachloride; D006899:Mixed Function Oxygenases; D001189:Aryl Hydrocarbon Hydroxylases; D065637:Cytochrome P-450 CYP2A6