Inhibition of ornithine decarboxylase activity by 2,3,7,8-tetrachlorodibenzo-p-dioxin.

Inhibition of ornithine decarboxylase activity by 2,3,7,8-tetrachlorodibenzo-p-dioxin.
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2,3,7,8-四氯二苯并-p-二恶英抑制鸟氨酸脱羧酶活性。

DOI:
10.1016/0006-2952(82)90613-x
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发表时间:
1982
影响因子:
5.8
通讯作者:
Russell,DH
Russell,DH
中科院分区:
医学2区
文献类型:
--
作者:
Potter,CL;Sipes,IG;Russell,DH

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研究了2,3,7,8-四氯二苯并二恶英(TCDD)对大鼠肝脏鸟氨酸脱羧酶(ODC)活性的影响。部分肝切除术后 16 小时,用 TCDD 预处理 1 周的大鼠表现出 ODC 活性增加 3 至 4 倍,而载体​​对照表现出 8 至 10 倍的增加。 TCDD对ODC诱导的这种抑制是时间依赖性的,因为在部分肝切除术时施用TCDD不会对随后的ODC诱导产生抑制作用。给予氨茶碱或地塞米松(分别通过cAMP介导的和直接核事件起作用的药剂)后ODC的诱导也被TCDD预处理所抑制。结论是,TCDD 预处理降低了肝脏对激素刺激的反应能力,这反映在 ODC 诱导的减弱上。 RNA 聚合酶 I 活性与生长和发育中的 ODC 活性呈正相关,随着 ODC 诱导的减少而降低。在未刺激的肝脏中,TCDD 1 周后,RNA 聚合酶 I 活性以及蛋白质、DNA 和 RNA 水平保持不变。然而,TCDD 给药导致腐胺和亚精胺的肝脏浓度降低,但精胺没有降低。这表明 TCDD 预处理会导致激素反应性随时间下降。
The effects of 2,3,7,8-tetrachlorodibenzo-pdioxin (TCDD) on the activity of rat liver ornithine decarboxylase (ODC) were investigated. Sixteen hours after partial hepatectomy, rats that had been pretreated with TCDD for 1 week exhibited a 3- to 4-fold increase in ODC activity, while vehicle controls exhibited an 8- to 10-fold increase. This inhibition of ODC induction by TCDD was time dependent since TCDD administration at the time of partial hepatectomy did not produce inhibitory effects on the subsequent ODC induction. ODC induction after either aminophylline or dexamethasone administration, agents which act via cAMP-mediated and direct nuclear events, respectively, also was inhibited by pretreatment with TCDD. It was concluded that TCDD pretreatment decreased the ability of the liver to respond to hormonal stimulation as reflected in the attenuation of ODC induction. RNA polymerase I activity, which positively correlates with ODC activity in growth and development, decreased concomitantly with decreased induction of ODC. In unstimulated liver, RNA polymerase I activity, as well as protein, DNA, and RNA levels, remained unchanged 1 week after TCDD. However, TCDD administration resulted in decreased liver concentrations of putrescine and spermidine, but not spermine. This suggests that TCDD pretreatment results in a time-dependent decrease in hormone responsivity.
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