TCDD ALTERS MEDIAL EPITHELIAL-CELL DIFFERENTIATION DURING PALATOGENESIS
TCDD ALTERS MEDIAL EPITHELIAL-CELL DIFFERENTIATION DURING PALATOGENESIS
复制标题
DOI：
10.1016/0041-008x(89)90010-0
复制
发表时间：
1989-06-15
影响因子：
3.8
通讯作者：
BIRNBAUM, LS
中科院分区：
文献类型：
--
作者：
ABBOTT, BD;BIRNBAUM, LS
2，3，7，8-四氯二苯并对二恶英（TCDD）是一种广泛分布的持久性环境污染物，对小鼠具有致畸性，可导致小鼠肾积水和腭裂。妊娠第10天或第12天暴露后，已证明裂开的发生率具有剂量依赖性，尽管胚胎在DG 12更敏感。TCDD暴露的腭架满足，但不融合，和程序性细胞死亡的中膜上皮细胞受到抑制。在早期的研究中还没有研究过四氯二苯并对二恶英改变中膜细胞发育程序的作用机制，也不知道这种机制是否与暴露的剂量或发育阶段无关。在该研究中，C57 BL/6 N小鼠（一种对TCDD敏感的品系）在GD 10或12口服给予溶于10 ml玉米油/kg中的0、6、12、24或30 μ g/kg体重。在GD 14、15或16检查胚胎腭架。评价腭闭合程度、上皮表面形态、细胞超微结构、[3 H]TdR掺入、EGF受体表达和125 I-EGF结合。在GD 10或12暴露后，TCDD改变了中膜上皮细胞的分化途径。腭架的大小和整体形态正常，但没有发生融合的中间上皮细胞的相对货架。TCDD阻止了中膜周细胞的程序性细胞死亡。表皮生长因子受体的中膜细胞的表达持续到第16天，并且受体能够结合配体。中膜细胞分化为复层、鳞状、角化上皮。在GD 10或12暴露后，表型转变为口腔样上皮。在较低剂量（6 μ g/kg）下，产生了发热腭裂，但那些确实有反应的搁架在分化上具有完全表达的转变。无论暴露开始于GD 10或12，或者剂量水平是否在一窝中仅产生少数腭裂，TCDD通过改变中膜细胞的分化程序产生腭裂。
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a widely distributed, persistent environmental contaminant that is teratogenic in mice, where it induces hydronephrosis and cleft palate. The incidence of clefting has been shown to be dose dependent after exposure on either gestation Day (GD) 10 or 12, although the embryo is more susceptible on DG 12. TCDD-exposed palatal shelves meet but do not fuse, and programmed cell death of the medial epithelial cells is inhibited. The mechanism of action through which TCDD alters the program of medial cell development has not been examined in earlier studies, and it is not known whether the mechanism is the same regardless of the dose or developmental stage of exposure. In this study, C57BL/6N mice, a strain sensitive to TCDD, were dosed orally on GD 10 or 12 with 0, 6, 12, 24, or 30 .mu.g/kg body wt, in 10 ml corn oil/kg. Embryonic palatal shelves were examiend on GD 14, 15, or 16. The degree of palatal closure, epithelial surface morphology, and cellular ultrastructure, the incorporation of [3H]TdR, the expression of EGF receptors, and the binding of 125I-EGF were assessed. After exposure on GD 10 or 12, TCDD altered the differentiation pathway of the medial epithelial cells. The palatal shelves were of normal size and overall morphology, but fusion of the medial epithelia of the opposing shelves did not occur. TCDD prevented programmed cell death of the medial peridermal cells. The expression of EGF receptors by medial cells continued through Day 16 and the receptors were able to bind ligand. The medial cells differentiated into a stratified, squamous, keratinizng epithelium. The shift in phenotype to an oral-like epithelium occurred after exposure on either GD 10 or 12. At the lower dose (6 .mu.g/kg), fever cleft palates were produced, but those shelves which did respond had a fully expressed shift in differentiation. Whether the exposure begins on GD 10 or 12 or whether the dosing level produces only a few cleft palates within a litter, TCDD produced cleft palate by altering the differentiation program of the medial cells.