Cell-specific expression of CYP2A5 in the mouse respiratory tract: effects of olfactory toxicants.
We performed a detailed analysis of mouse cytochrome P450 2A5 (CYP2A5) expression by in situ hybridization (ISH) and immunohistochemistry (IHC) in the respiratory tissues of mice. The CYP2A5 mRNA and the corresponding protein co-localized at most sites and were predominantly detected in the olfactory region, with an expression in sustentacular cells, Bowman's gland, and duct cells. In the respiratory and transitional epithelium there was no or only weak expression. The nasolacrimal duct and the excretory ducts of nasal and salivary glands displayed expression, whereas no expression occurred in the acini. There was decreasing expression along the epithelial linings of the trachea and lower respiratory tract, whereas no expression occurred in the alveoli. The hepatic CYP2A5 inducers pyrazole and phenobarbital neither changed the CYP2A5 expression pattern nor damaged the olfactory mucosa. In contrast, the olfactory toxicants dichlobenil and methimazole induced characteristic changes. The damaged Bowman's glands displayed no expression, whereas the damaged epithelium expressed the enzyme. The CYP2A5 expression pattern is in accordance with previously reported localization of protein and DNA adducts and the toxicity of some CYP2A5 substrates. This suggests that CYP2A5 is an important determinant for the susceptibility of the nasal and respiratory epithelia to protoxicants and procarcinogens.
Piras
Elena
E
Department of Pharmaceutical Biosciences, Uppsala University, SE-751 24 Uppsala, Sweden.
Franzén
Anna
A
Fernández
Estíbaliz L
EL
Bergström
Ulrika
U
Raffalli-Mathieu
Françoise
F
Lang
Matti
M
Brittebo
Eva B
EB
D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000096:biosynthesis*; D065637:Cytochrome P-450 CYP2A6; D000072467:Cytochrome P450 Family 2; D004785:Environmental Pollutants / Q000633:toxicity*; D004790:Enzyme Induction; D005260:Female; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D008713:Methimazole / Q000633:toxicity; D051379:Mice; D008811:Mice, Inbred DBA; D006899:Mixed Function Oxygenases / Q000096:biosynthesis*; D009301:Nasolacrimal Duct / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009570:Nitriles / Q000633:toxicity; D009831:Olfactory Mucosa / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010634:Phenobarbital / Q000633:toxicity; D011720:Pyrazoles / Q000633:toxicity; D012137:Respiratory System / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D012469:Salivary Glands / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
D004785:Environmental Pollutants; D009570:Nitriles; D011720:Pyrazoles; C031280:pyrazole; D008713:Methimazole; D006899:Mixed Function Oxygenases; D001189:Aryl Hydrocarbon Hydroxylases; C585520:Cyp2a5 protein, mouse; D065637:Cytochrome P-450 CYP2A6; D000072467:Cytochrome P450 Family 2; C055869:dichlobanil; D010634:Phenobarbital