Nguyen-Ba G, Robert S, Lasne C, Ventura L, Chouroulinkov I, van Kreijl C F, van Steeg H, Truhaut R
Laboratoire de Pharmacologie Cellulaire, I.C.I.G., Villejuif.
C R Acad Sci III. 1992;314(11):485-92.
The mechanism of ornithine decarboxylase (ODC) induction by phorbol ester (TPA) has been studied in two permanent epithelial cell lines, a control (Ctr) and a Benzo (a) pyrene transformed line (BaP-tr); the degree of ODC gene expression (ODC-mRNA) was evaluated in comparison to the ODC activity. A small dose of TPA (4 x 10(-8) M) highly induced ODC activity in these cells. The induction levels differed however, corresponding respectively to 4:1 (induced: basal ODC) in Ctr cells and to 2:1 in BaP-tr cells. This difference reflected the variation of ODC gene expression; the ODC-mRNA induction was 6:1 in Ctr cells and 3:1 in BaP-tr cells. Repetitive TPA treatment decreased the ODC induction in these cells, as compared to that resulting from a single TPA treatment. Studies of ODC modulation were performed in presence of anti-inflammatory agents. In the two cell lines, Indomethacin (anti-cyclooxygenase) did not change the level of ODC induction by TPA. Nordihydroguaiaretic acid (NDGA, anti-lipoxygenase) inhibited this induced ODC. These results differed from that obtained in vivo in mouse skin. Dexamethasone (DXME, anti-phospholipase A2) showed different action according to treatment time. Used together with TPA (t0), DXME inhibited ODC induction by the carcinogen; with three hours delay after TPA (t3), DXME treatment stimulated ODC in the cells. This divergent action may be reproduced by Actinomycin D, while Cycloheximide only exhibited constant inhibition. Studies now in progress suggested that the inhibition of TPA induced ODC by DXME may reflect ODC gene repression, as for the stimulating effect it could be related to ODC post-transcriptional modulation, owing to the decrease of proteolytic action.
已在两种永久性上皮细胞系（一种对照细胞系（Ctr）和一种苯并（a）芘转化细胞系（BaP-tr））中研究了佛波酯（TPA）诱导鸟氨酸脱羧酶（ODC）的机制；与ODC活性相比，评估了ODC基因表达程度（ODC-mRNA）。小剂量的TPA（4×10⁻⁸ M）在这些细胞中高度诱导ODC活性。然而，诱导水平有所不同，在Ctr细胞中分别为4:1（诱导型：基础ODC），在BaP-tr细胞中为2:1。这种差异反映了ODC基因表达的变化；在Ctr细胞中ODC-mRNA诱导为6:1，在BaP-tr细胞中为3:1。与单次TPA处理相比，重复TPA处理降低了这些细胞中的ODC诱导。在存在抗炎剂的情况下进行了ODC调节研究。在这两种细胞系中，吲哚美辛（抗环氧化酶）未改变TPA诱导的ODC水平。去甲二氢愈创木酸（NDGA，抗脂氧合酶）抑制这种诱导的ODC。这些结果与在小鼠皮肤体内获得的结果不同。地塞米松（DXME，抗磷脂酶A2）根据处理时间表现出不同的作用。与TPA一起使用（t0）时，DXME抑制致癌物诱导的ODC；在TPA处理三小时后（t3），DXME处理刺激细胞中的ODC。放线菌素D可重现这种不同的作用，而环己酰亚胺仅表现出持续的抑制作用。目前正在进行的研究表明，DXME对TPA诱导的ODC的抑制可能反映了ODC基因的抑制，至于刺激作用，可能与转录后调节有关，这是由于蛋白水解作用的降低。
