Activation and toxicity of bromobenzene in nasal tissues in mice

Abstract

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.

Survey Anatomy of the Paranasal Sinuses in the Normal Mouse

“…Our group and others have evaluated at the effects of nasal foreign bodies. Brittebo et al 12 demonstrated the toxic effects of bromobenzine on the nasal tissues of mice, whereas Wiethoff et al 13 used magnetic resonance imaging to identify and serially follow mucosal injury in mice exposed to 3 methylindole. We have since reported the osteogenic potential of esterified hyaluronic acid nasal packing material 14 …”

Olfactory Toxicity of Methimazole: Dose-Response and Structure-Activity Studies and Characterization of Flavin-Containing Monooxygenase Activity in the Long-Evans Rat Olfactory Mucosa

“…It (8). Still others (e.g., 3,3'-iminodipropionitrile, 3-methylindole, 2,6-dichlorobenzonitrile, nitrosamines, bromobenzene, acetaminophen) cause olfactory mucosal damage following iv or ip injection (2,4,10,12,25). While the role of blood flow in regional deposition of such compounds as the mechanism underlying the site specificity of lesion development is currently under investigation (18) (27,30 (20,21 ).…”

Purification and characterization of two unique forms of cytochrome P-450 from rabbit nasal microsomes

“…As reviewed recently (Black & Coon, 1986, 1987, more than 60 P-450s have been purified to electrophoretic homogeneity from various species, mostly from liver microsomes. The tissue-specific distribution of some of these isozymes has been established.…”

“…The P-450-dependent metabolism of a variety of substances in nasal mucosa (Ding et al, 1986;Brittebo, 1982Brittebo, , 1987Brittebo et al, 1983;Lofberg & Tjalve, 1984;Brittebo & Rafter, 1984;Dahl & Brezinski, 1985;Reed et al, 1986;Longo et al, 1986) may be related to the ability of the organism to maintain olfactory sensitivity (Dahl et al, 1982) as well as to the susceptibility of this particular tissue to the toxic effects of many foreign compounds . A striking feature of the monooxygenase system of the nasal mucosa is that its catalytic activity, expressed as the turnover number for total P-450, is much higher than that of hepatic microsomes with many substrates, such as butanol (Ding et al, 1986), hexamethylphosphoramide (HMPA)' (Dahl & Brezinski, 1985), or ethoxycoumarin (Reed et al, 1986).…”