促癌物TPA诱导小鼠表皮鸟氨酸脱羧酶mRNA表达和维甲类化合物对该表达的影响

Increased Expression of Ornithine Decarboxylase mRNA Induced by Tumor Promoter 12-O-tetradecanoylphorbol-13-acetate and the Effect of Retinoid R8605 on this Expression in Mouse Epidermis

強皮肤促癌物十四烷酰佛波醋酸酯(TPA)局部应用时可触发一系列的生物化学改变,其中最明显的事件之一就是对ODC活性的短暂而急到的诱导,而这种诱导作用与其促癌作用密切相关。利用Northern印迹分析和条带(Slot)印迹分析证明,10nmol/L TPA一次局部处理小鼠背部皮肤可刺激ODC mRNA(2.0kb大小)表达,在4h左右最为明显,随后逐渐降低。10nmol/L TPA多次处理小鼠皮肤(每2天一次,共4次)也有类似的促进作用,但却在6h左右最为明显。在二甲基苯蒽和巴豆油诱发的二阶段小鼠皮肤乳头瘤和癌组织中也观察到了相同大小的ODC mRNA的高水平表达,尤以癌组织最高。新维甲类化合物R8605虽能明显抑制巴豆油诱导的ODC活性,但却未见对TPA诱导的ODC mRNA增加有明显抑制作用。

Topical applieation of mouse skin with the potent tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) results in an array of biochemical alterations, one of the earliest being a transient and rapid induction of epidermal ornithine decarboxylase (ODC) activity which correlates well with its tumor promoting ability. Northern blot and Slot blot analysis of mRNA isolated from mouse epidermis after a single TPA(10 nmol/L)treatment revealed the stimulation of one species of ODC mRNA of 2.0kb with a maximum at about 4h. The same size species of ODC mRNA was detected 3—6 h after multiple treatment with TPA (once every two days for 4 times)as well as in 7, 12-dimethylbenz[a] anthracene (DMBA) /croton oil-induced mouse papillomas and carcinomas not treated with croton oil for 2 months. The expression of ODC mRNA in carchnomas was more obvious than that in papillomas which seems to be related to the degree of tumor malignance. New retinoid R8605 which significantly inhibited the croton oil-induced ODC activity, did not show inhibitory effect on the TPA-stimulated ODC mRNA expression.