Localization and induction of cytochrome P450 1A1 and aryl hydrocarbon hydroxylase activity in rat nasal mucosa.
Cytochrome P450 1A1 was localized immunohistochemically and benzo[a]pyrene hydroxylase activity was identified in situ by means of fluorescence histochemistry in the nasal mucosa of untreated, 3-methylcholanthrene-treated or Aroclor 1254-treated rats. Cytochrome P450 1A1 was localized predominantly within Bowman's glands, with considerably less staining occurring in the olfactory epithelium of untreated rats. Similarly, benzo[a]pyrene was hydroxylated to the greatest extent in Bowman's glands and, to a lesser extent, in olfactory epithelial cells. Pre-treatment of tissue sections of nasal mucosa with anti-P450 1A1 inhibited most of the benzo[a]pyrene hydroxylase activity present. Although 3-methylcholanthrene treatment did not affect either cytochrome P450 1A1 or hydroxylase activity in the nasal mucosa, a single intraperitoneal injection of Aroclor 1254 significantly increased anti-P450 1A1 binding in Bowman's glands and in the olfactory and respiratory epithelia, and dramatically enhanced benzo[a]pyrene hydroxylase activity in the epithelia and the subepithelial ducts and glands in both the olfactory and respiratory regions. In contrast to its effects on cytochrome P450 1A1, Aroclor 1254 produced a considerably greater induction of hydroxylase activity in the respiratory region, especially in the seromucous glands, than in the olfactory region. These results suggest that Aroclor 1254 treatment also induces other forms of cytochrome P450 in the respiratory region of the nasal mucosa.
Voigt
J M
JM
Department of Pharmacology, University of Iowa, Iowa City.
Guengerich
F P
FP
Baron
J
J
D000818:Animals; D001140:Aroclors / Q000494:pharmacology; D001579:Benzopyrene Hydroxylase / Q000096:biosynthesis / Q000378:metabolism*; D020111:Chlorodiphenyl (54% Chlorine); D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis / Q000378:metabolism*; D004790:Enzyme Induction; D007124:Immunoenzyme Techniques; D007527:Isoenzymes / Q000096:biosynthesis / Q000378:metabolism*; D008297:Male; D008748:Methylcholanthrene / Q000494:pharmacology; D009297:Nasal Mucosa / Q000201:enzymology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D001140:Aroclors; D007527:Isoenzymes; D020111:Chlorodiphenyl (54% Chlorine); D008748:Methylcholanthrene; D003577:Cytochrome P-450 Enzyme System; D001579:Benzopyrene Hydroxylase