Nondetectable concentrations of human placental Ah receptors are associated with potent induction of microsomal benzo[a]pyrene hydroxylase in individuals exposed to polychlorinated biphenyls, quaterphenyls, and dibenzofurans.
Human exposure to polychlorinated biphenyls, quaterphenyls, and dibenzofurans occurred in an accidental food poisoning episode in Taiwan in 1979. Our objective was to evaluate the role of Ah receptors in the production of biochemical effects detected in placentas from exposed subjects. Placentas were obtained from pregnant women who were identified from a registry of exposed individuals. Benzo[a]pyrene (BaP) hydroxylase was quantified in placental microsomes and Ah receptor was investigated in placental cytosolic and nuclear fractions by a variety of receptor-binding techniques using 2,3,7,8-[1,6-3H]tetrachlorodibenzo-p-dioxin ([3H]TCDD) as the ligand. Microsomal BaP hydroxylase was dramatically elevated in placentas of exposed subjects compared to those of nonexposed, nonsmoking control subjects. However, concentrations of displaceable [3H]TCDD binding in placental preparations from exposed or control subjects were uniformally low; approximately 1.0 fmol/mg cytosolic protein. Further evaluation of displaceable TCDD binding by sucrose-gradient sedimentation and hydroxylapatite column chromatography revealed that binding properties were different than those for the Ah receptor. These data suggest that extremely low concentrations of Ah receptors in human placenta may be sufficient to markedly elevate microsomal BaP hydroxylation. Alternatively, induction in human placenta may be mediated by a mechanism not requiring Ah receptor.
D000293:Adolescent; D000328:Adult; D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000096:biosynthesis*; D001579:Benzopyrene Hydroxylase / Q000096:biosynthesis*; D002499:Centrifugation, Density Gradient; D002851:Chromatography, High Pressure Liquid; D003600:Cytosol / Q000378:metabolism; D004790:Enzyme Induction; D005260:Female; D006801:Humans; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism*; D011078:Polychlorinated Biphenyls / Q000378:metabolism*; D000072317:Polychlorinated Dibenzodioxins / Q000378:metabolism; D011247:Pregnancy; D011257:Pregnancy Proteins / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D000072317:Polychlorinated Dibenzodioxins; D011257:Pregnancy Proteins; D011078:Polychlorinated Biphenyls; D001579:Benzopyrene Hydroxylase; D001189:Aryl Hydrocarbon Hydroxylases