Cytochrome P450 2B1 immunoreactivity in bronchiolar and alveolar epithelial cells after exposure of rats to ozone.
Pulmonary cytochrome P450 (P450) plays an important role in the metabolism of xenobiotics. We have previously demonstrated that exposure to ozone (O3), a major oxidant of photochemical smog, increases P450 content and xenobiotic metabolizing activities in the rat lung. Therefore, it is conceivable that O3 exposures modify the pattern and potency of xenobiotic metabolism. The aim of this study is to examine the effect of O3 exposure on localization of P450 in the lung. After exposure of rats to 0.4 ppm O3 for 14 days, the concentration of P450 2B1, the main isozyme of P450 in the lung, increased to 214% of the control value. By immunohistochemical analyses, O3 exposure caused hypertrophy and hyperplasia of P450 2B1-positive non-ciliated bronchiolar epithelial (Clara) cells, showing an increase in the cell number to 128% of the control level. At the proximal alveoli, O3 exposure induced hypertrophic epithelial cells that presented immunoreactivity to P450 2B1 and morphological characteristics of both type 1 and type 2 cells. These hypertrophic cells had lamellar inclusion bodies, microvilli, and extended cytoplasm. Typical type 2 cells did not react with anti-P450 2B1 antibody even after O3 exposure. These data suggest that O3 exposure may activate the P450-mediated xenobiotic metabolism in the pulmonary epithelial cells, and that expression of P450 2B1 in the pulmonary epithelial cells might be regulated by the factors involved in the process of the differentiation from type 2 to type 1 cells.
Takahashi
Y
Y
Environmental Health Sciences Division, National Institute for Environmental Studies, Ibaraki, Japan.
Aida
S
S
Suzuki
E
E
Ito
Y
Y
Miura
T
T
Kimula
Y
Y
D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases; D015153:Blotting, Western; D001980:Bronchi / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D002452:Cell Count / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D003577:Cytochrome P-450 Enzyme System / Q000187:drug effects / Q000378:metabolism*; D004847:Epithelial Cells; D004848:Epithelium / Q000187:drug effects / Q000201:enzymology; D006965:Hyperplasia / Q000139:chemically induced; D006984:Hypertrophy / Q000139:chemically induced; D007150:Immunohistochemistry; D008297:Male; D008854:Microscopy, Electron; D016253:Microscopy, Immunoelectron; D010126:Ozone / Q000633:toxicity*; D011650:Pulmonary Alveoli / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D051381:Rats; D017208:Rats, Wistar; D013047:Specific Pathogen-Free Organisms; D013250:Steroid Hydroxylases / Q000187:drug effects / Q000378:metabolism*
D010126:Ozone; D003577:Cytochrome P-450 Enzyme System; D013250:Steroid Hydroxylases; D001189:Aryl Hydrocarbon Hydroxylases; C025619:steroid 16-beta-hydroxylase