Disposition of 3H-aflatoxin B1 in mice: formation and retention of tissue bound metabolites in nasal glands.
Whole-body autoradiography with 3H-labelled aflatoxin B1 (3H-AFB1) in C57B1-mice showed a pronounced accumulation and retention of radioactivity in some nasal glands. At long survival intervals the labelling of the nasal glands was much higher than that of the liver. Experiments in vitro showed a capacity of the nasal glands to form tissue-bound 3H-AFB1-metabolites. Incubations in the presence of glutathione decreased the levels of tissue-bound 3H-AFB1-metabolites both in the liver and in the nasal glands, but the decrease was more pronounced in the former than in the latter tissue. The 3H-AFB1-metabolite-binding to the nasal glands in vitro was inhibited by the cytochrome P-450-inhibitor metyrapone and by CO- and N2-atmospheres indicating a cytochrome P-450-dependent bioactivation of the AFB1 in these glands. Cytochrome P-450 was shown to be present in the glands although at a much lower level than in the liver. The glands in the nose, which were shown to have this AFB1-metabolizing capacity, were the lateral nasal gland (Steno's gland) situated ventrally and laterally to the maxillary sinus and the large group of glands in the lateral nasal wall ventrally to the ostium of the maxillary sinus. Our results also indicated an AFB1-metabolizing capacity of the serous glands which are present in the anterior part of the nasal septum.
Larsson
P
P
Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Swedish University of Agricultural Sciences, Uppsala Biomedical Centre.
Hoedaya
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WI
Tjälve
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D016604:Aflatoxin B1; D000348:Aflatoxins / Q000378:metabolism / Q000493:pharmacokinetics*; D000818:Animals; D001345:Autoradiography; D002273:Carcinogens / Q000378:metabolism / Q000493:pharmacokinetics*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D005088:Exocrine Glands / Q000378:metabolism*; D005260:Female; D005978:Glutathione / Q000494:pharmacology; D008099:Liver / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009297:Nasal Mucosa / Q000378:metabolism*; D011485:Protein Binding; D013997:Time Factors
D000348:Aflatoxins; D002273:Carcinogens; D003577:Cytochrome P-450 Enzyme System; D016604:Aflatoxin B1; D005978:Glutathione