CHARACTERIZATION OF THE PEAK PERIOD OF SENSITIVITY FOR THE INDUCTION OF HYDRONEPHROSIS IN C57BL/6N MICE FOLLOWING EXPOSURE TO 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN
CHARACTERIZATION OF THE PEAK PERIOD OF SENSITIVITY FOR THE INDUCTION OF HYDRONEPHROSIS IN C57BL/6N MICE FOLLOWING EXPOSURE TO 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN
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DOI：
10.1016/0272-0590(90)90171-f
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发表时间：
1990-07-01
期刊：
影响因子：
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通讯作者：
BIRNBAUM, LS
中科院分区：
文献类型：
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作者：
COUTURE, LA;HARRIS, MW;BIRNBAUM, LS
2,3,7,8，-四氯二苯并对二恶英（TCDD）是一种对小鼠非常有效的致畸原。小鼠暴露于TCDD和其他结构相关的多卤芳烃后，肾积水和腭裂是最敏感的致畸指标。尽管半衰期相对较长，但研究人员已经确定了C57BL/6N小鼠诱导腭裂的关键窗口期。为观察肾致畸关键期，将妊娠C57BL/6N小鼠灌胃1次，剂量0 ~ 24 .mu。妊娠第6、8、10、12或14天，每公斤体重g TCDD。在妊娠第18天处死所有母鼠，检查胎儿是否存在肾积水和腭裂。在所有日子里，母亲的肝体重比显著高于对照组，而母亲的体重增加不受影响。仅在24亩时，胎儿死亡率相对于对照组有所增加。g TCDD/kg对照组和tcdd组胎儿体重无显著差异。从GD 6到GD 12，腭裂的发生率呈剂量相关性增加，并且确定GD 12是诱发硬腭裂的关键窗口。在所有剂量水平下均观察到肾积水，与暴露日无关，在3 .mu时发生率接近100%。妊娠第12天及更早服用更高剂量。在第14天的所有剂量下，相对于其他所有天，肾积水的发生率和严重程度都降低了。肾脏病变的严重程度每天都有剂量相关的增加，但在GD 6和12之间，严重程度是不变的。因此，虽然在孕龄6至12之间，腭对TCDD的敏感性随着胎龄的增加而增加，但这些天之间肾积水的发展没有差异。然而，数据表明，在妊娠第14天，尿路对TCDD的敏感性可能较低。
2,3,7,8,-Tetrachlorodibenzo-p-dioxin (TCDD) is an extremely potent teratogen in mice. Hydronephrosis and cleft palate are the most sensitive measures of teratogenicity in mice following exposure to TCDD and other structurally related polyhalogenated aromatic hydrocarbons. Despite a relatively long half-life, investigators have identified a critical window for the induction of cleft palate in C57BL/6N mice. To characterize the critical period for renal teratogenesis, pregnant C57BL/6N mice were treated once by gavage with 0-24 .mu.g TCDD/kg body wt on Gestation Day (GD) 6, 8, 10, 12, or 14. All dams were killed on GD 18, and the fetuses were examined for the presence of hydronephrosis and cleft palate. Maternal liver-to-body weight ratios were significantly elevated above controls on all days, while maternal weight gain was unaffected. Fetal mortality was increased relative to controls only at 24 .mu.g TCDD/kg on GD 6. There was no significant difference in fetal body weights between control and TCDD-treated fetuses. The incidence of cleft palate increased in a dose-related fashion from GD 6 to GD 12, and identification of GD 12 as the critical window for induction of clefting of the hard palate was confirmed. Hydronephrosis was observed at all dose levels, regardless of exposure day, and the incidence was close to 100% at 3 .mu.g TCDD/kg and higher doses on GD 12 and earlier. At all doses on GD 14, both the incidence and severity of hydronephrosis were decreased relative to all other days. There was a dose-related increase in the severity of the renal lesion on each day, but between GD 6 and 12 severity was constant. Thus, while palatal sensitivity to TCDD increased with gestational age between GD 6 and 12, there was no difference among these days in development of hydronephrosis. The data suggest, however, that on GD 14 the urinary tract may be less sensitive to TCDD.