Metabolism-dependent activation and toxicity of chemicals in nasal glands.
The mucosae of the nasal passages contain a large amount of glands which express secretory proteins as well as phase I and phase II biotransformation enzymes. In this review the metabolic activation, covalent binding and toxicity of chemicals in the Bowman's glands in the olfactory mucosa, in the sero-mucous glands in the nasal septum and in the lateral nasal glands and maxillary glands around the maxillary sinuses are discussed. Light microscopic autoradiographic studies have demonstrated a selective covalent binding of nasal toxicants and carcinogens such as halogenated hydrocarbons and N-nitrosamines, especially in the Bowman's glands following a single systemic exposure, suggesting a high rate of metabolic activation of chemicals in these glands. Special attention is put on the herbicide dichlobenil which induces necrosis in the olfactory mucosa following a cytochrome-P450-mediated metabolic activation and covalent binding in the Bowman's glands.
Brittebo
E B
EB
Department of Pharmaceutical Biosciences, Uppsala University, Sweden. eva.brittebo@tox.uu.se
D000818:Animals; D001549:Benzamides / Q000633:toxicity; D001711:Biotransformation; D002273:Carcinogens / Q000633:toxicity*; D005088:Exocrine Glands / Q000378:metabolism; D006540:Herbicides / Q000633:toxicity; D006801:Humans; D051379:Mice; D009297:Nasal Mucosa / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D009300:Nasal Septum / Q000378:metabolism; D009570:Nitriles; D051381:Rats; D015262:Xenobiotics / Q000633:toxicity*
D001549:Benzamides; D002273:Carcinogens; D006540:Herbicides; D009570:Nitriles; D015262:Xenobiotics; C055869:dichlobanil