Valsta L M, Hendricks J D, Bailey G S
Department of Food Science and Technology, Oregon State University, Corvallis 97331.
Food Chem Toxicol. 1988 Feb;26(2):129-35. doi: 10.1016/0278-6915(88)90109-3.
Rainbow trout are known to be more susceptible to aflatoxin B1 (AFB1) hepatocarcinogenesis than coho salmon, or trout pre-fed the carcinogenesis inhibitors beta-naphthoflavone (beta NF), Aroclor 1254 or indole-3-carbinol. The study reported here examined the relationship between AFB1-glutathione (GSH) conjugation and AFB1 carcinogenesis in salmon, trout and trout pre-fed the three inhibitors. The AFB1-glutathione (AFB1-SG) conjugate was not detected in salmon bile and was present in trout bile in amounts representing less than 0.2% of the administered dose 24 hr after injection of [3H]AFB1. The major conjugates were glucuronides of aflatoxicol and aflatoxicol M1. In incubations of isolated liver cell fractions, less than 0.5% of the original AFB1 dose was recovered as AFB1-SG in salmon and trout preparations, compared to 25% in mouse-liver cell preparations. The GSH concentration in livers of the control trout was higher than that for coho salmon but lower than that for trout pre-fed beta NF. Liver GSH-transferase activity in control trout livers was much higher than in the control salmon livers, but was only 62% of that found for trout fed beta NF. There was no apparent relationship among the various groups between liver GSH concentrations, liver GSH-transferase activity, or biliary GSH conjugate, and the degree of carcinogenic response of AFB1. Thus current evidence does not indicate a major role for aflatoxin B1 epoxide-GSH detoxification in coho salmon, or rainbow trout fed any of the three anticarcinogens tested. These results in salmonid fish are contrary to those which suggest AFB1-SG conjugation as a major determinant of AFB1 carcinogenesis and its dietary modulation in rodent models.
已知虹鳟比银大麻哈鱼或预先投喂致癌抑制剂β-萘黄酮（β-NF）、多氯联苯混合物1254或吲哚-3-甲醇的虹鳟更容易受到黄曲霉毒素B1（AFB1）诱导的肝癌发生。本文报道的研究考察了AFB1与谷胱甘肽（GSH）结合反应和AFB1在大麻哈鱼、虹鳟以及预先投喂三种抑制剂的虹鳟体内致癌作用之间的关系。在注射[3H]AFB1后24小时，大麻哈鱼胆汁中未检测到AFB1-谷胱甘肽（AFB1-SG）结合物，虹鳟胆汁中存在的结合物量占给药剂量的比例不到0.2%。主要的结合物是黄曲霉毒素醇和黄曲霉毒素醇M1的葡糖醛酸苷。在分离的肝细胞组分培养中，在大麻哈鱼和虹鳟制剂中，回收的作为AFB1-SG的原始AFB1剂量不到0.5%，而在小鼠肝细胞制剂中为25%。对照虹鳟肝脏中的GSH浓度高于银大麻哈鱼，但低于预先投喂β-NF的虹鳟。对照虹鳟肝脏中的GSH转移酶活性远高于对照大麻哈鱼肝脏，但仅为投喂β-NF的虹鳟的62%。在不同组之间，肝脏GSH浓度、肝脏GSH转移酶活性或胆汁GSH结合物与AFB1的致癌反应程度之间没有明显关系。因此，目前的证据并不表明黄曲霉毒素B1环氧化物-GSH解毒在银大麻哈鱼或投喂三种测试抗癌剂中任何一种的虹鳟中起主要作用。鲑科鱼类的这些结果与那些表明AFB1-SG结合是啮齿动物模型中AFB1致癌作用及其饮食调节的主要决定因素的结果相反。
