Olfactory cytochrome P-450 immunoreactivity in mice is altered by dichlobenil but preserved by metyrapone.
Antibodies to cytochromes P-450NMa and P-450NMb (CYP2A and CYP2G1, respectively) (P-450 nomenclature by Nebert et al., DNA Cell Biol. 10, 1- (1-14) 14, 1991) were used to assess the effects of the herbicide dichlobenil on the distribution of these olfactory-specific isozymes in the olfactory mucosa. Twenty-eight hours after a single dose (12 mg/kg) of dichlobenil, characteristic regions of the olfactory mucosa showed signs of necrosis in H&E stained sections. Accompanying this was a dramatic reduction in P-450 immunoreactivity in Bowman's glands of the olfactory mucosa, and an apparent redistribution of P-450 immunoreactivity within sustentacular cells. Treatment of mice with metyrapone, a P-450 inhibitor, at 10 min prior to and 2, 4, 6, and 8 h after a single dichlobenil injection, provided some protection against the damaging effects of dichlobenil. Both the gross and subcellular appearance of P-450 immunoreactivity in metyrapone/dichlobenil treated mice was similar to controls. Western blot analysis of P-450 expression following dichlobenil or metyrapone/dichlobenil treatment was generally consistent with immunohistochemical findings. These studies support previous reports that dichlobenil-induced olfactotoxicity is cytochrome P-450 mediated.
Walters
E
E
Division of Biological Sciences, University of Missouri, Columbia 65211.
Buchheit
K
K
Maruniak
J A
JA
D000818:Animals; D001549:Benzamides / Q000633:toxicity*; D015153:Blotting, Western; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000032:analysis / Q000187:drug effects*; D005260:Female; D006540:Herbicides / Q000633:toxicity*; D007150:Immunohistochemistry; D008797:Metyrapone / Q000494:pharmacology*; D051379:Mice; D008815:Mice, Inbred Strains; D009570:Nitriles; D009831:Olfactory Mucosa / Q000187:drug effects* / Q000201:enzymology* / Q000473:pathology
D001549:Benzamides; D065607:Cytochrome P-450 Enzyme Inhibitors; D006540:Herbicides; D009570:Nitriles; D003577:Cytochrome P-450 Enzyme System; C055869:dichlobanil; D008797:Metyrapone