Dose requirements, assay procedures and tissue specificity for PCB inductation of P-450 dependent mono-oxygenase activity in the rat: implications for design of studies measuring in vivo induction of human placental mono-oxygenases.
Pregnant Sprague-Dawley and Fisher 344 rats were treated on day 15 of gestation with Aroclor 1254 in a single dose ranging from 0 to 500 mg kg-1 body weight and killed on day 18 of gestation. In the small groups of animals used for this study, no effect was observed on mean maternal liver or placental weight, or the number of fetal resorptions at any of the doses tested. Measurement of aryl hydrocarbon hydroxylase (AHH) and 7-ethoxycoumarin O-deethylase (7ECD) activity in tissue homogenates, however, showed that administration of Aroclor 1254 (15 mg kg-1 body weight or greater) induced mono-oxygenase activity in fetal liver. Both the AHH and 7ECD assay detected effects of PCBs with similar sensitivity, and the findings were comparable when homogenates were assayed instead of microsomes. These data were used to suggest technical approaches to the detection of mono-oxygenase induction in placental tissue human populations exposed to PCBs.
D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000096:biosynthesis; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis*; D004790:Enzyme Induction / Q000187:drug effects; D005260:Female; D005333:Fetus / Q000378:metabolism; D007700:Kinetics; D008099:Liver / Q000201:enzymology; D008861:Microsomes / Q000201:enzymology; D008862:Microsomes, Liver / Q000201:enzymology; D006899:Mixed Function Oxygenases / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D009929:Organ Size / Q000187:drug effects; D010920:Placenta / Q000201:enzymology*; D011078:Polychlorinated Biphenyls / Q000378:metabolism / Q000494:pharmacology*; D011247:Pregnancy; D051381:Rats; D011916:Rats, Inbred F344; D011919:Rats, Inbred Strains; D012098:Reproduction / Q000187:drug effects
D003577:Cytochrome P-450 Enzyme System; D011078:Polychlorinated Biphenyls; D006899:Mixed Function Oxygenases; D001189:Aryl Hydrocarbon Hydroxylases