HEPATIC AND EXTRAHEPATIC BIOACTIVATION AND GSH CONJUGATION OF AFLATOXIN B-1 IN SHEEP

Whole-body autoradiography of [H-3]aflatoxin B-1 ([H-3]AFB(1)) in lamb showed a localization of bound labelling, in addition to the liver, i n the nasal olfactory and respiratory mucosa, in the mucosa of the nas opharynx, pharynx, oesophagus, larynx, trachea, bronchi and bronchiole s and in the palpebral and bulbar conjunctiva. Microautoradiography re vealed that the bound material was confined to specific cell types in extrahepatic tissues. Whole-body autoradiography also showed a labelli ng of pigmented tissues (such as the eye melanin), which can be ascrib ed to a melanin affinity of AFB(1). In vivo experiments, performed wit h microsomal preparations of tissues from ewe and lamb showed that sev eral of the extrahepatic tissues were more efficient than the liver in forming DNA-bound AFB(1) metabolites. The nasal olfactory mucosa was by far the most effective tissue in this respect. AFB(1) induced a hig h number of gene mutations in Salmonella typhimurium TA100 when incuba ted with supernatant preparations (9000 g) of the nasal olfactory muco sa, whereas incubations with preparations of the liver resulted in a l ower effect. It has been reported that AFB, can induce nasal tumours i n sheep. When microsomal preparations of various tissues were incubate d in the presence of reduced glutathione (GSH), but without any additi on of cytosolic glutathione-S-transferase (GST), a drastic decrease in the AFB(1)-DNA binding was seen. Analyses of the water-soluble metabo lites formed in the microsomal incubations supplemented with GSH showe d fluorescent and ninhydrin-positive metabolites that were not present in the absence of GSH. These results indicate that sheep tissues have intrinsic microsomal GST or cytosolic GSTs associated with the micros omal fraction with a high capacity to catalyse the conjugation of bioa ctivated AFB(1) to GSH. The results of the present study show that sev eral extrahepatic tissues of sheep have a potent capacity to bioactiva te AFB(1) and also a high capacity to GSH conjugate the bioactivated A FB(1).