TCDD TERATOGENICITY--MODULATION IN MIXTURES

TCDD(2，3，7，8-四氯二苯并-对二恶英)已被证明是 多种物种高度致畸，导致腭裂(CP) 和小鼠肾积水(HN)，无明显剂量 母体或胎儿毒性。此响应可用作一种方法 确定化合物是否是二恶英类化合物。这个 几种多氯代二苯并呋喃(PCDF)与 某些含有TCDD的多氯联苯(PCB)是添加剂。 然而，非平面的多氯联苯异构体2，4，5，2‘，4’，5‘- 六氯联苯(HCB)可拮抗Cp的诱导 TCDD，只有非常窄的窗口-8000-33000倍于六氯联苯 作为TCDD。我们没有观察到HN的任何抑制作用。事实上，卡布拉·巴赫 1000 mg/kg可单独诱发HN。妊娠小鼠的治疗 与TCDD和维甲酸(RA)一起使用会导致 慢性前列腺炎的发生率。然而，RA并不影响TCDD诱导的 HN的发病率，TCDD也不会改变RA诱导的发病率 肢芽异常。当RA与TCDD上瘾地相互作用时 治疗是在怀孕10天(Gd)进行的，然而，互动是 氢化可的松(HC)也能增强GD12的作用。 当与TCDD联合应用时，CP的发生率。因此，TCDD 可与内源性生长因子相互作用导致胎儿 异常现象。TCDD是一种大鼠的发育毒素。近在咫尺 相关化合物2，3，4，7，8-五氯二苯并呋喃未能 给药后第8、10或12天的Fischer大鼠出现HN 剂量高达300杯/公斤，其中广泛的孕产妇和胎儿 确实发生了毒性和CP。这是否与母体有关 毒性或对TCDD的特异性仍有待确定。

TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin) has been shown to be highly teratogenic in multiple species, causing cleft palate (CP) and hydronephrosis (HN) in the mouse at doses with no overt maternal or fetal toxicity. This response can be used as a method of determining whether compounds are dioxin-like or not. The interaction of several polychlorinated dibenzofurans (PCDFs) and certain polychlorinated biphenyls (PCBs) with TCDD are additive. However, the nonplanar PCB isomer, 2,4,5,2',4',5'- hexachlorobiphenyl (HCB), can antagonize the induction of CP by TCDD, only in a very narrow window - 8000-33000 times as much HCB as TCDD. We have not observed any inhibition of HN. In fact, HCB at 1000mg/kg may induce HN by itself. Treatment of pregnant mice with TCDD and retinoic acid (RA) causes an increase in the incidence of CP. However, RA does not affect the TCDD-induced incidence of HN, nor does TCDD alter the incidence of RA-induced limb bud abnormalities. RA interacts addictively with TCDD when treatment is on gestation day (gd) 10, however, the interaction is synergistic on gd 12. Hydrocortisone (HC) can also enhance the incidence of CP when given in combination with TCDD. Thus, TCDD can interact with endogenous-type growth factors to cause fetal abnormalities. TCDD is a developmental toxin in rats. The closely related compound, 2,3,4,7,8-pentachlorodibenzofuran, failed to cause HN in Fischer rats when administered on gd 8, 10, or 12 at doses as high as 300 mug/kg where extensive maternal and fetal toxicity and CP did occur. Whether this is related to maternal toxicity or is specific to TCDD remains to be determined.