Kensler T W, Busby W F, Davidson N E, Wogan G N
Biochim Biophys Acta. 1976 Jun 23;437(1):200-10. doi: 10.1016/0304-4165(76)90361-5.
The effect of aflatoxin B1 on the binding capacity of rat liver cytoplasmic glucocorticoid receptors and the nuclear binding of the activated receptor complex was investigated. No alterations in the kinetics of [3H]desamethasone-cytosol receptor complex formation were noted 2 h after treatment with 1 mg/kg aflatoxin B1. However, a 33% decrease in the concentration of nuclear acceptor sites and a 24% decrease in the glucocorticoid receptor-nuclear binding equilibrium constant of dissociation was observed. This response was near maximal at 2 h and persisted for at least 26 h. Inhibition of nuclear binding capacity was directly related to aflatoxin B1 dose, with a correlation coefficient of 0.99. Actinomycin D treatment (0.1 mg/kg) resulted in a slight reduction (16%) in the concentration of nuclear acceptor sites but had no effect on the nuclear binding dissociation constant. Administration of [3H]dexamethasone to alfatoxin B1 -treated rats produced a similar pattern of glucocorticoid binding distribution in vivo to that observed in vitro. No differences in [3H]dexamethasone-cytoplasmic receptor binding between control and alfatoxin B1 -treated rats were found, whereas nuclear [3H]dexanthasone binding was reduced 34% by alfatoxin B1 -treatment.
研究了黄曲霉毒素B1对大鼠肝脏细胞质糖皮质激素受体结合能力以及活化受体复合物核结合的影响。用1mg/kg黄曲霉毒素B1处理2小时后，未观察到[3H]地塞米松-胞质溶胶受体复合物形成动力学的改变。然而，观察到核受体位点浓度降低了33%，糖皮质激素受体-核结合解离平衡常数降低了24%。这种反应在2小时时接近最大值，并持续至少26小时。核结合能力的抑制与黄曲霉毒素B1剂量直接相关，相关系数为0.99。放线菌素D处理（0.1mg/kg）导致核受体位点浓度略有降低（16%），但对核结合解离常数没有影响。给黄曲霉毒素B1处理的大鼠注射[3H]地塞米松后，体内糖皮质激素结合分布模式与体外观察到的相似。在对照大鼠和黄曲霉毒素B1处理的大鼠之间，未发现[3H]地塞米松-细胞质受体结合有差异，而黄曲霉毒素B1处理使核[3H]地塞米松结合减少了34%。
