Hassoun E A, Bagchi D, Stohs S J
Dept. of Pharmacology, College of Pharmacy, University of Toledo, OH 43606, USA.
Res Commun Mol Pathol Pharmacol. 1996 Nov;94(2):157-69.
TCDD, endrin and lindane induce an oxidative stress and enhance lipid peroxidation in fetal and placental tissues of mice. The levels of the products resulting from altered lipid metabolism, including malondialdehyde (MDA), formaldehyde (FA), acetaldehyde (ACT) and acetone (ACON) have been determined in maternal sera and amniotic fluids of pregnant C57BL/6J and DBA/2J mice after oral administration of single fetotoxic doses of TCDD, endrin and lindane on day 12 of gestation, using high pressure liquid chromatography (HPLC). Under these conditions, TCDD given at a dose of 30 micrograms/kg body weight to C57BL/6J mice produced 2.5-3.9 and 1.7-4.0 fold increases in the levels of the four metabolites in maternal sera and the amniotic fluids, respectively. TCDD given to DBA/2J mice at a dose of 60 micrograms/kg produced 1.5-1.7 and 1.7-2.2 fold increases in the levels of these metabolites in maternal sera and the amniotic fluids, respectively. Endrin, when given at a dose of 4.5 mg/kg body weight to either mouse strain, produced increases of 1.9-3.1 and 1.7-3.2-fold in the levels of the four metabolites in maternal sera and the amniotic fluids, respectively, in the C57BL/6J mice and increases of 1.4-1.6 and 1.2-1.5 fold in the levels of these metabolites in maternal sera and the amniotic fluids, respectively, in the DBA/2J mice. Lindane given at a dose of 30 mg/kg body weight to C57BL/6J mice produced 1.5-2.0 and 1.3-1.7-fold increases in the four metabolites in maternal serum and amniotic fluids, respectively, while administration of this same dose to DBa/2J mice produced 1.2-1.5 and 1.1-1.5 fold increases, respectively. Increases in the levels of lipid metabolites occur in maternal serum and amniotic fluid as a result of enhanced lipid peroxidation in response to TCDD, endrin and lindane. Lipid peroxidation may participate in the fetotoxic effects of these xenobiotics and these effects are observed regardless of the Ah-responsiveness of the mice, although higher levels of the metabolites are produced by TCDD in Ah-responsive mice.
2,3,7,8-四氯二苯并对二恶英（TCDD）、异狄氏剂和林丹可诱导小鼠胎儿及胎盘组织产生氧化应激并增强脂质过氧化作用。在妊娠第12天给怀孕的C57BL/6J和DBA/2J小鼠经口给予单一胎儿毒性剂量的TCDD、异狄氏剂和林丹后，利用高压液相色谱法（HPLC）测定了母体血清和羊水中脂质代谢改变所产生的产物水平，包括丙二醛（MDA）、甲醛（FA）、乙醛（ACT）和丙酮（ACON）。在这些条件下，给C57BL/6J小鼠按30微克/千克体重的剂量给予TCDD后，母体血清和羊水中四种代谢产物的水平分别升高了2.5至3.9倍和1.7至4.0倍。给DBA/2J小鼠按60微克/千克的剂量给予TCDD后，母体血清和羊水中这些代谢产物的水平分别升高了1.5至1.7倍和1.7至2.2倍。给任一品系小鼠按4.5毫克/千克体重的剂量给予异狄氏剂后，C57BL/6J小鼠母体血清和羊水中四种代谢产物的水平分别升高了1.9至3.1倍和1.7至3.2倍，DBA/2J小鼠母体血清和羊水中这些代谢产物的水平分别升高了1.4至1.6倍和1.2至1.5倍。给C57BL/6J小鼠按30毫克/千克体重的剂量给予林丹后，母体血清和羊水中四种代谢产物的水平分别升高了1.5至2.0倍和1.3至1.7倍，而给DBA/2J小鼠给予相同剂量后，分别升高了1.2至1.5倍和1.1至1.5倍。由于对TCDD、异狄氏剂和林丹产生反应，脂质过氧化增强，导致母体血清和羊水中脂质代谢产物水平升高。脂质过氧化可能参与了这些外源性物质的胎儿毒性作用，并且无论小鼠的芳烃反应性如何，均可观察到这些作用，尽管TCDD在芳烃反应性小鼠中产生的代谢产物水平更高。
