Distribution of microsomal epoxide hydrolase and glutathione S-transferase in the rat olfactory mucosa: relevance to distribution of lesions caused by systemically-administered olfactory toxicants.
This study represents part an of ongoing effort to understand the mechanism underlying the distribution of the olfactory mucosal lesion resulting from the systemic administration of compounds such as 2,6-dichlorobenzonitrile (dichlobenil) and beta,beta'-iminodipropionitrile (IDPN). Immunohistochemistry was performed to localize the microsomal form of epoxide hydrolase (mEH) and glutathione S-transferase (GST) isozymes alpha, mu and pi in the rodent olfactory mucosa. GST-pi was found in abundance in the Bowman's glands of the mucosa lining the dorsal medial meatus (DMM) of the nasal cavity and in the nuclei of basal and sustentacular cells of the dorsal and lateral nasal cavity. Liver and olfactory mucosal levels of mEH are equivalent by Western blot analysis. mEH appeared to be localized in the apical cytoplasm of sustentacular cells in all regions of the olfactory mucosa except for the epithelium lining the DMM. These observations, coupled with the known profile of metabolites for dichlobenil, suggest that systemically-administered compounds causing site-specific lesions in the epithelium lining the DMM of the nasal cavity may do so by the in situ production of reactive epoxide metabolites which are then poorly capable of being detoxified. Thus, the distribution of metabolic enzymes, rather than the absolute level of an enzyme in a tissue, may dictate lesion distribution in the case of toxicants which are bioactivated in target tissues.
Genter
M B
MB
Department of Toxicology, North Carolina State University, Raleigh 27695-7633, USA.
Owens
D M
DM
Deamer
N J
NJ
D000818:Animals; D015153:Blotting, Western; D001932:Brain Neoplasms / Q000139:chemically induced* / Q000201:enzymology; D004851:Epoxide Hydrolases / Q000032:analysis* / Q000378:metabolism; D005982:Glutathione Transferase / Q000032:analysis* / Q000378:metabolism; D007150:Immunohistochemistry; D008658:Inactivation, Metabolic; D007527:Isoenzymes / Q000032:analysis* / Q000378:metabolism; D008297:Male; D008861:Microsomes / Q000201:enzymology; D009498:Neurotoxins / Q000493:pharmacokinetics / Q000633:toxicity; D009570:Nitriles / Q000493:pharmacokinetics / Q000633:toxicity*; D009831:Olfactory Mucosa / Q000187:drug effects / Q000201:enzymology* / Q000648:ultrastructure; D051381:Rats; D011919:Rats, Inbred Strains; D014018:Tissue Distribution
D007527:Isoenzymes; D009498:Neurotoxins; D009570:Nitriles; C008110:3,3'-iminodipropionitrile; D005982:Glutathione Transferase; D004851:Epoxide Hydrolases; C055869:dichlobanil