Effects of butylated hydroxytoluene pretreatment on the metabolism and genotoxicity of aflatoxin B1 in primary cultures of adult rat hepatocytes: selective reduction of nucleic acid binding.
Effects of butylated hydroxytoluene pretreatment on the metabolism and genotoxicity of aflatoxin B1 in primary cultures of adult rat hepatocytes: selective reduction of nucleic acid binding.
复制标题
丁基羟基甲苯预处理对成年大鼠肝细胞原代培养物中黄曲霉毒素 B1 代谢和遗传毒性的影响：选择性减少核酸结合。
DOI：
10.1016/0041-008x(84)90354-5
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发表时间：
1984
影响因子：
3.8
通讯作者：
Byard,JL
中科院分区：
文献类型：
--
作者：
Salocks,CB;Hsieh,DP;Byard,JL
为了阐明二丁基羟基甲苯（BHT）抗癌活性的生化机制，研究了BHT预处理对原代培养大鼠肝细胞中黄曲霉毒素B1（AFB1）代谢和遗传毒性的影响。在10天的预处理期间，成年雄性大鼠喂食对照饲料或添加0.5% BHT的饲料。随后从每只动物中分离肝细胞，并在化学成分确定的培养基中培养。从喂食BHT的大鼠制备的培养物比对照组代谢AFB1更快。BHT预处理也能促进AFB1氧化为黄曲霉毒素M1（AFM1），加快AFM1的结合速度。在BHT预处理的培养物中，与DNA和RNA的共价结合分别减少了91%和82%，而蛋白质结合仅减少了29%。在BHT预处理的培养物中，AFB1没有刺激可检测的DNA修复合成，尽管在对照培养物中DNA修复的刺激是明显的。在一项单独的实验中，在BHT预处理的细胞中观察到持续较高的还原型谷胱甘肽基线浓度，表明BHT预处理可能增强AFB1的解毒型谷胱甘肽结合物的形成。这些结果表明，BHT的抗癌活性部分是由于优先增强肝脏解毒机制，结果是细胞内活性代谢物浓度降低，形成更少的共价结合加合物。
To elucidate biochemical mechanisms underlying the anticarcinogenic activity of butylated hydroxytoluene (BHT), studies were undertaken to characterize the influence of BHT pretreatment on the metabolism and genotoxicity of aflatoxin B1(AFB1) in primary cultures of rat hepatocytes. During a 10-day pretreatment period, adult male rats were fed either a control diet or a diet supplemented with 0.5% BHT. Hepatocytes were subsequently isolated from each animal and cultured in chemically defined medium. Cultures prepared from rats which had been fed BHT metabolized AFB1more rapidly than did controls. BHT pretreatment also enhanced oxidation of AFB1to aflatoxin M1(AFM1), and accelerated the rate of AFM1conjugation. Covalent binding to DNA and RNA in BHT-pretreated cultures was reduced by 91 and 82%, respectively, while protein binding decreased by only 29%. AFB1did not stimulate detectable DNA repair synthesis in BHT-pretreated cultures, although stimulation of DNA repair was clearly evident in control cultures. In a separate experiment, consistently higher baseline concentrations of reduced glutathione were observed in BHT-pretreated cells, indicating that BHT pretreatment may enhance formation of detoxified glutathione conjugates of AFB1. These findings suggest that the anticarcinogenic activity of BHT is due in part to preferential enhancement of hepatic detoxification mechanisms, with the result that intracellular concentrations of reactive metabolites are reduced and fewer covalently bound adducts are formed.