Wiebel F J, Cikryt P
GSF-Institute of Toxicology, Gesellschaft für Strahlen- und Umweltforschung, Neuherberg/München, F.R.G.
Chem Biol Interact. 1990;76(3):307-20. doi: 10.1016/0009-2797(90)90098-8.
The synergistic effect of dexamethasone (DEX) and polycyclic aromatic hydrocarbons on the induction of cytochrome P450IA1 (P450IA1) was examined in H4IIEC3/T Reuber hepatoma cells. P450IA1 activity was determined by the hydroxylation of benzo[a]pyrene (AHH) and deethylation of 7-ethoxyresorufin (EROD). The amount of Ah receptor, i.e. the specific cytosolic binding protein of 3-methylcholanthrene or 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in H4IIEC3/T cells was characterized and quantitated by high performance gel filtration. Benz[a]anthracene and TCDD induced AHH and EROD activities, respectively, about 20-fold within 4 h. The increase was about 100-fold when cells were pretreated with DEX. The glucocorticoid alone induced P450IA1 activities 3-4 fold. DEX elicited half maximum AHH induction at a concentration of 20 nM in the presence or absence of benz[a]anthracene. Maximal potentiation of AHH induction required treatment with DEX for at least 32 h prior to the exposure to benz[a]anthracene. Treatment of H4IIEC3/T cells with DEX for 20 h caused a 2-3-fold increase in the amount of Ah receptor. The results suggest that the synergistic effect of DEX and polycyclic aromatic hydrocarbons on P450IA1 induction involves a time-consuming process which may consist of the synthesis or modification of a factor, possibly the Ah receptor.
在地鼠肾细胞系H4IIEC3/T中研究了地塞米松（DEX）与多环芳烃对细胞色素P450IA1（P450IA1）诱导的协同效应。通过苯并[a]芘的羟基化作用（AHH）和7-乙氧基异吩恶唑酮的脱乙基作用（EROD）来测定P450IA1的活性。通过高效凝胶过滤对H4IIEC3/T细胞中Ah受体的量，即3-甲基胆蒽或2,3,7,8-四氯二苯并-对-二恶英（TCDD）的特异性胞质结合蛋白进行表征和定量。苯并[a]蒽和TCDD分别在4小时内诱导AHH和EROD活性增加约20倍。当细胞用DEX预处理时，增加约100倍。单独的糖皮质激素诱导P450IA1活性增加3至4倍。在存在或不存在苯并[a]蒽的情况下，DEX在20 nM浓度时引起AHH诱导的半数最大值。AHH诱导的最大增强需要在暴露于苯并[a]蒽之前用DEX处理至少32小时。用DEX处理H4IIEC3/T细胞20小时导致Ah受体量增加2至3倍。结果表明，DEX与多环芳烃对P450IA1诱导的协同效应涉及一个耗时的过程，该过程可能包括一种因子（可能是Ah受体）的合成或修饰。
