Hepatic and extrahepatic bioactivation and GSH conjugation of aflatoxin B1 in sheep

Whole-body autoradiography of ³H]aflatoxin B₁ (³H]AFB₁ inlamb showed a localization of bound labelling, in addition tothe liver, in the nasal olfactory and respiratory mucosa, inthe mucosa of the nasopharynx, pharynx, oesophagus, larynx,trachea, bronchi and bronchioles and in the palpebral and bulbarconjunctiva. Microautoradiography revealed that the bound materialwas confined to specific cell types in extrahepatic tissues.Whole-body autoradiography also showed a labelling of pigmentedtissues (such as the eye melanin), which can be ascribed toa melanin affinity of AFB₁ In vivo experiments, performed withmicrosomal preparations of tissues from ewe and lamb showedthat several of the extrahepatic tissues were more efficientthan the liver in forming DNA-bound AFB₁ metabolites. The nasalolfactory mucosa was by far the most effective tissue in thisrespect. AFB, induced a high number of gene mutations in Salmonellatyphimurium TA100 when incubated with super natant preparations(9000 g) of the nasal olfactory mucosa, whereas incubationswith preparations of the liver resulted in a lower effect. Ithas been reported that AFB₁ can induce nasal tumours in sheep.When microsomal preparations of various tissues were incubatedin the presence of reduced glutathione (GSH), but without anyaddition of cytosolic glutathione-S-transferase (GST), a drasticdecrease in the AFB₁-DNA binding was seen. Analyses of the water-solublemetabolites formed in the microsomal incubations supple mentedwith GSH showed fluorescent and ninhydrin-positive metabolitesthat were not present in the absence of GSH. These results indicatethat sheep tissues have intrinsic microsomal GST or cytosolicGSTs associated with the microsomal fraction with a high capacityto catalyse the conjugation of bioactivated AFB₁ to GSH. Theresults of the present study show that several extrahepatictissues of sheep have a potent capacity to bioactivate AFB₁and also a high capacity to GSH conjugate the bioactivated AFB₁.