Bioactivation of aflatoxin B1 in the nasal and tracheal mucosa in swine.
Whole-body autoradiography of 3H-labeled aflatoxin B1 in young pigs showed a localization of bound label in the nasal olfactory and respiratory mucosa, in the tracheo-laryngeal mucosa, and in the conjunctiva, in addition to the liver. Whole-body and microautoradiography also showed a labeling of pigmented tissues, which can be ascribed to a melanin binding of AFB1. In vitro experiments with microsomal preparations of various tissues from sows revealed that the nasal respiratory and olfactory mucosa had the highest capacity to form DNA-bound aflatoxin B1-metabolites. The tracheal mucosa and the liver, in order, had lesser binding capacity. The lung was found to be devoid of aflatoxin B1-bioactivating capacity. In vitro microautoradiography revealed bound label in specific cell types in the nose and trachea and in some cells of the conjunctiva. A drastic decrease in the aflatoxin B1-DNA binding was observed when microsomal preparations of the nasal respiratory and olfactory mucosa were incubated in the presence of reduced glutathione, but without any addition of cytosolic glutathione-S-transferases. In incubations of liver microsomes under these conditions a somewhat lower inhibition of the aflatoxin B1-DNA binding was seen. Our results demonstrate that the nasal olfactory and respiratory mucosa and the tracheal mucosa have a higher capacity than the liver to bioactivate aflatoxin B1 in swine. Our data further show that microsomal-associated glutathione-S-transferases with a high capacity to catalyze the conjugation of the reactive aflatoxin B1-epoxide to reduced glutathione are present in the nasal olfactory and respiratory mucosa of swine.
Larsson
P
P
Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Swedish University of Agricultural Sciences, Uppsala, Sweden.
Tjälve
H
H
D016604:Aflatoxin B1 / Q000032:analysis / Q000378:metabolism / Q000493:pharmacokinetics*; D000818:Animals; D001345:Autoradiography / Q000662:veterinary; D001711:Biotransformation; D003228:Conjunctiva / Q000737:chemistry / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D005260:Female; D005978:Glutathione / Q000032:analysis / Q000378:metabolism; D008099:Liver / Q000737:chemistry / Q000378:metabolism; D009092:Mucous Membrane / Q000737:chemistry / Q000378:metabolism; D009297:Nasal Mucosa / Q000737:chemistry / Q000378:metabolism*; D009831:Olfactory Mucosa / Q000737:chemistry / Q000378:metabolism; D013552:Swine / Q000378:metabolism* / Q000502:physiology; D014132:Trachea / Q000737:chemistry / Q000378:metabolism*; D014316:Tritium
D014316:Tritium; D004247:DNA; D016604:Aflatoxin B1; D005978:Glutathione