TCDD, ENDRIN AND LINDANE INDUCED INCREASES IN LIPID METABOLITES IN MATERNAL SERA AND AMNIOTIC FLUIDS OF PREGNANT C57BL 6J AND DBA/2J MICE/

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 malondial dehyde (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 fetotoxi c doses of TCDD, endrin and lindane on day 12 of gestation, using high pressure liquid chromatography (HPLC). Under these conditions, TCDD g iven at a dose of 30 mu g/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 mu g/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 a nd 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 incre ases 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 mi ce. Lindane given at a dose of 30 mg/kg body weight to C57BL/6J mice p roduced 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 in creases, respectively. Increases in the levels of lipid metabolites oc cur in maternal serum and amniotic fluid as a result of enhanced lipid peroxidation in response to TCDD, endrin and lindane. Lipid peroxidat ion 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 ofthe metabolites are produced by TCDD in Ah-responsive mice.