Weston W M, Nugent P, Greene R M
Department of Pathology, Anatomy, and Cell Biology, Thomas Jefferson University, Philadelphia, PA 19107.
Biochem Biophys Res Commun. 1995 Feb 15;207(2):690-4. doi: 10.1006/bbrc.1995.1242.
The polychlorinated aromatic hydrocarbon 2,3,7,8-tetrachlorodibenzo-p-dioxin, commonly referred to as dioxin or TCDD, has been shown to cause cleft palate in mice. TCDD displays an interesting interaction with another cleft palate teratogen, retinoic acid (RA): when mice are treated with TCDD and RA simultaneously, palatal clefts can be observed in 100% of offspring of mothers at dose levels far below those required for either agent to produce clefting if given singly. This synergy strongly suggests that the pathways controlled by these agents converge at one or more points in cells of the developing palate. In this study, we examined the effects of TCDD on induction of the type II cellular retinoic acid binding protein (CRABP-II) and the retinoic acid receptor beta (RAR beta) by RA in murine embryonic palate mesenchyme (MEPM) cells. While TCDD alone had no effect on basal levels of expression of either gene, the induction of both genes by RA was strongly inhibited by TCDD. These results represent the first evidence for a direct molecular interaction between the RA and TCDD-mediated signaling pathways.
多氯代芳烃2,3,7,8 - 四氯二苯并 - 对 - 二噁英，通常被称为二噁英或TCDD，已被证明会导致小鼠腭裂。TCDD与另一种腭裂致畸剂视黄酸（RA）表现出有趣的相互作用：当同时用TCDD和RA处理小鼠时，在远低于单独给予任何一种药剂产生腭裂所需剂量水平的情况下，可在100%的母鼠后代中观察到腭裂。这种协同作用强烈表明，这些药剂所控制的途径在发育中的腭部细胞的一个或多个点上汇聚。在本研究中，我们检测了TCDD对视黄酸（RA）在小鼠胚胎腭间充质（MEPM）细胞中诱导II型细胞视黄酸结合蛋白（CRABP-II）和视黄酸受体β（RARβ）的影响。虽然单独的TCDD对这两种基因的基础表达水平没有影响，但RA对这两种基因的诱导被TCDD强烈抑制。这些结果代表了RA和TCDD介导的信号通路之间直接分子相互作用的首个证据。
