Postnatal stimulation of hepatic microsomal enzymes following administration of TCDD to pregnant rats.
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) administered to pregnant rats at 3 mu-g/kg as a single oral dose during early, middle, or late gestation caused marked elevations of some maternal hepatic microsomal enzymes for at least 10 weeks after treatment. This dose was not teratogenic and fetal rates of glucuronidation of testosterone and p-nitrophenol (PNP) were unaffected. Increases in fetal liver benzpyrene hydroxylase (BPH) activities were evident during late gestation although cytochrome P-450 and cytochrome b-5 contents were unchanged. The offspring of pregnant rats administered TCDD had markedly elevated hepatic PNP UDP-glucuronyltransferase (UDPGT) BPH, and microsomal cytochrome contents whereas the perinatal development of testosterone UDPGT was unchanged. PNP glucuronidation attained a maximal 8-fold increase above controls by 3 weeks after birth and activities were twice that of controls 8 weeks after birth (adults). Maximal increases in benzpyrene hydroxylation rates occurred one day after birth when in the prenatally exposed group activities were approximately 20 times higher than controls. Foster mother experiments demonstrated that the postnatal inductive effect resulted both from exposure of newborns to TCDD via maternal milk and the activation of an inducing mechanism occurring after birth. Tese data demonstrate that multiple factors are responsible for the induction of hepatic microsomal enzymes in the newborn following administration of TCDD to pregnant rats.
D000818:Animals; D000831:Animals, Newborn; D001580:Benzopyrenes; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D003580:Cytochromes / Q000378:metabolism; D004147:Dioxins / Q000494:pharmacology*; D004790:Enzyme Induction / Q000187:drug effects; D005260:Female; D005865:Gestational Age; D005966:Glucuronidase / Q000378:metabolism; D014453:Glucuronosyltransferase / Q000378:metabolism; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology*; D006899:Mixed Function Oxygenases / Q000378:metabolism; D009596:Nitrophenols; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology*; D011247:Pregnancy; D051381:Rats; D013739:Testosterone; D013997:Time Factors
D001580:Benzopyrenes; D003580:Cytochromes; D004147:Dioxins; D009596:Nitrophenols; D000072317:Polychlorinated Dibenzodioxins; D013739:Testosterone; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D014453:Glucuronosyltransferase; D005966:Glucuronidase