Activation and toxicity of bromobenzene in nasal tissue in mice.
Autoradiography of mice injected i.v. with bromobenzene-14C (BB; 25 mumol/kg body wt) revealed a high concentration of non-volatile metabolites in the olfactory mucosa and in the glands around the maxillary sinuses. As determined with solvent-extracted tissue sections, there was a high level of irreversibly bound metabolites in the Bowman's glands in the olfactory mucosa, while the level of bound metabolites was low in the glands around the maxillary sinuses. Histopathological examination of the nose region of mice given a single i.p. dose of unlabelled BB (greater than or equal to 4.8 mmol/kg body wt) revealed degeneration and necrosis of the glands of Bowman. Degenerative changes in the olfactory epithelium were also observed. Moreover, focal degeneration and necrosis were found in the lateral nasal glands (greater than or equal to 4.8 mmol/kg body wt). Cyst-like dilatation of acini was observed in the lateral nasal glands and in the maxillary glands located around the maxillary sinus. Incubation of BB (26 microM) with a homogenate prepared from the olfactory mucosa revealed an irreversible binding, which clearly exceeded that of the liver. It is suggested that BB is activated in situ to a cytotoxic metabolite that reacts with the glands of Bowman. The specific toxicity observed in the lateral nasal glands correlated with a high concentration of non-volatile but extractable metabolites in these glands.
Brittebo
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EB
Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Swedish University of Agricultural Sciences, Uppsala.
Eriksson
C
C
Brandt
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I
D000818:Animals; D001345:Autoradiography / Q000379:methods; D001969:Bromobenzenes / Q000633:toxicity*; D056486:Chemical and Drug Induced Liver Injury; D005260:Female; D008099:Liver / Q000473:pathology; D008443:Maxillary Sinus / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009297:Nasal Mucosa / Q000187:drug effects*; D009831:Olfactory Mucosa / Q000187:drug effects / Q000473:pathology
D001969:Bromobenzenes; C032036:bromobenzene