Transplacental induction of carcinogen-hydroxylating systems with 2,3,7,8-tetrachlorodibenzo-p-dioxin

The effects of a highly toxic herbicide contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) upon rates of hydroxylation of N-2-fluorenylacetamide (FAA) and of benzo[a]-pyrene (BP) were studied in fetal livers, in placentas, maternal livers, and adrenal glands of pregnant Sprague-Dawley rats. Aryl hydrocarbon hydroxylase (AHH) activity was increased 14- and 100-fold in maternal and fetal livers, respectively, but only minimal increases were observed in placentas and adrenal glands. Similar results were obtained with respect to rates of 7-, 5-, N-, 3-, and 1-hydroxylations of FAA. Histologic examinations revealed extensive cellular damage in the placentas as well as pathologic changes in fetal and maternal livers. Electron microscopy indicated enlarged mitochondria and extensive glycogen deposition in maternal and fetal livers and increases in the amounts of rough endoplasmic reticulum in fetal livers. Analyses of BP metabolism with high-pressure liquid chromatography also revealed that the formation of diols (relative to phenols) was markedly increased in fetal and maternal livers following treatments with TCDD. The results suggested that the relative lack of response of fetal hepatic mixed-function oxidase systems to commonly employed inducing agents (polycyclic aromatic hydrocarbons) was not due to a lack of appropriate structural and/or regulatory genes required for the expression of enzyme induction during fetal life.