EMBRYOTOXICITY OF 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN (TCDD) - THE EMBRYONIC VASCULATURE IS A PHYSIOLOGICAL TARGET FOR TCDD-INDUCED DNA-DAMAGE AND APOPTOTIC CELL-DEATH IN MEDAKA (ORIZIAS LATIPES)

Vertebrate embryos are extremely sensitive to environmental contaminan ts known as planar halogenated hydrocarbons (PHHs). The physiological targets that mediate PHH-induced embryotoxicity are not known. We have characterized embryotoxicity in medaka (Orizias latipes) caused by 2, 3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), the prototypic PHH. DNA degr adation in cells of the embryonic vasculature and loss of functional i ntegrity of the medial yolk vein were demonstrated in TCDD-exposed emb ryos. Pharmacological intervention with piperonyl butoxide inhibited T CDD-induced DNA degradation, restored the functional integrity of the medial yolk vein, and protected against the embryotoxicity of TCDD. Tr eatment of TCDD-exposed embryos with the antioxidant N-acetylcysteine also provided significant protection against the embryotoxicity of TCD D. These results demonstrate that DNA damage and consequent cell death in the embryonic vasculature are key physiological mediators of TCDD- induced embryotoxicity. (C) 1996 Academic Press, Inc.