Hassoun E A, Stohs S J
School of Pharmacy and Allied Health Professions, Creighton University, Omaha, NE 68178, USA.
Comp Biochem Physiol C Pharmacol Toxicol Endocrinol. 1996 Mar;113(3):393-8. doi: 10.1016/0742-8413(96)00011-4.
The teratogenic effects of endrin and lindane have been determined and compared to those induced by TCDD in the fetuses of C57BL/6J and DBA/2J mice after the administration of single oral doses to pregnant mice on day 12 of gestation. TCDD produced dose-dependent decreases in fetal weight, fetal thymic weight and placental weight, and dose-dependent increases in fetolethality, cleft palate formation and hydronephrosis at doses of 10-30 and 30-60 micrograms/kg body weight in C57BL/6J and DBA/2J mice, respectively. No maternal death was observed at the given doses in both strains of mice. Endrin (4.5 and 6 mg/kg body weight) and lindane (30 and 45 mg/kg body weight) produced significant decreases in fetal weight and placental weight in C57BL/6J and DBA/2J mice, and dose-dependent decreases in fetal thymic weight in C57BL/6J mice but not DBA/2J mice. Endrin and lindane caused 0-25 and 14-25% maternal deaths, respectively, at the above mentioned doses. Neither cleft plate nor hydronephrosis were induced by endrin or lindane in the two strains of mice. The results support the hypothesis that TCDD-induced cleft plate and hydronephrosis involve mechanisms that are Ah (aryl hydrocarbon) receptor mediated. However, other fetotoxic effects induced by TCDD, and the fetotoxic effects induced by endrin and lindane may involve additional unknown mechanisms that are not related to the Ah-receptor.
在妊娠第12天给C57BL/6J和DBA/2J小鼠的怀孕母鼠单次口服给药后，已确定了异狄氏剂和林丹的致畸作用，并与2,3,7,8-四氯二苯并对二恶英（TCDD）对这些小鼠胎儿所诱导的致畸作用进行了比较。在C57BL/6J和DBA/2J小鼠中，TCDD分别在剂量为10 - 30微克/千克体重和30 - 60微克/千克体重时，使胎儿体重、胎儿胸腺重量和胎盘重量呈剂量依赖性下降，同时使胎儿致死率、腭裂形成和肾积水呈剂量依赖性增加。在给定剂量下，两种品系的小鼠均未观察到母体死亡。异狄氏剂（4.5和6毫克/千克体重）和林丹（30和45毫克/千克体重）使C57BL/6J和DBA/2J小鼠的胎儿体重和胎盘重量显著下降，使C57BL/6J小鼠的胎儿胸腺重量呈剂量依赖性下降，但对DBA/2J小鼠无此作用。在上述剂量下，异狄氏剂和林丹分别导致0 - 25%和14 - 25%的母体死亡。异狄氏剂和林丹在这两种品系的小鼠中均未诱导腭裂或肾积水。结果支持这样的假设，即TCDD诱导的腭裂和肾积水涉及芳烃（Ah）受体介导的机制。然而，TCDD诱导的其他胎儿毒性作用，以及异狄氏剂和林丹诱导的胎儿毒性作用可能涉及与Ah受体无关的其他未知机制。
