Larsson P, Busk L, Tjälve H
Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Swedish University of Agricultural Sciences, Uppsala.
Carcinogenesis. 1994 May;15(5):947-55. doi: 10.1093/carcin/15.5.947.
Whole-body autoradiography of [3H]aflatoxin B1 ([3H]AFB1) in lamb showed a localization of bound labelling, in addition to the liver, in the nasal olfactory and respiratory mucosa, in the mucosa of the nasopharynx, pharynx, oesophagus, larynx, trachea, bronchi and bronchioles and in the palpebral and bulbar conjunctiva. Microautoradiography revealed that the bound material was confined to specific cell types in extrahepatic tissues. Whole-body autoradiography also showed a labelling of pigmented tissues (such as the eye melanin), which can be ascribed to a melanin affinity of AFB1. In vivo experiments, performed with microsomal preparations of tissues from ewe and lamb showed that several of the extrahepatic tissues were more efficient than the liver in forming DNA-bound AFB1 metabolites. The nasal olfactory mucosa was by far the most effective tissue in this respect. AFB1 induced a high number of gene mutations in Salmonella typhimurium TA100 when incubated with supernatant preparations (9000 g) of the nasal olfactory mucosa, whereas incubations with preparations of the liver resulted in a lower effect. It has been reported that AFB1 can induce nasal tumours in sheep. When microsomal preparations of various tissues were incubated in the presence of reduced glutathione (GSH), but without any addition of cytosolic glutathione-S-transferase (GST), a drastic decrease in the AFB1-DNA binding was seen. Analyses of the water-soluble metabolites formed in the microsomal incubations supplemented with GSH showed 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 microsomal fraction with a high capacity to catalyse the conjugation of bioactivated AFB1 to GSH. The results of the present study show that several extrahepatic tissues of sheep have a potent capacity to bioactivate AFB1 and also a high capacity to GSH conjugate the bioactivated AFB1.
[3H]黄曲霉毒素B1（[3H]AFB1）在羔羊体内的全身放射自显影显示，除肝脏外，结合标记还定位于鼻嗅觉和呼吸黏膜、鼻咽、咽、食管、喉、气管、支气管和细支气管黏膜以及睑结膜和球结膜。显微放射自显影显示，结合物质局限于肝外组织中的特定细胞类型。全身放射自显影还显示色素沉着组织（如眼黑色素）有标记，这可归因于AFB1对黑色素的亲和力。在体内实验中，用母羊和羔羊组织的微粒体制剂进行实验，结果表明，几种肝外组织在形成与DNA结合的AFB1代谢物方面比肝脏更有效。在这方面，鼻嗅觉黏膜是迄今为止最有效的组织。当与鼻嗅觉黏膜的上清液制剂（9000g）一起孵育时，AFB1在鼠伤寒沙门氏菌TA100中诱导了大量基因突变，而与肝脏制剂孵育则效果较低。据报道，AFB1可在绵羊中诱发鼻肿瘤。当各种组织的微粒体制剂在还原型谷胱甘肽（GSH）存在下孵育，但不添加任何胞质谷胱甘肽-S-转移酶（GST）时，可观察到AFB1与DNA的结合急剧减少。对添加GSH的微粒体孵育中形成的水溶性代谢物的分析显示，存在荧光和茚三酮阳性代谢物，而在没有GSH的情况下则不存在。这些结果表明，绵羊组织具有内在的微粒体GST或与微粒体部分相关的胞质GST，具有高催化生物活化的AFB1与GSH结合的能力。本研究结果表明，绵羊的几种肝外组织具有强大的生物活化AFB1的能力，并且也具有将生物活化的AFB1与GSH结合的高能力。
