Placental markers of human exposure to polychlorinated biphenyls and polychlorinated dibenzofurans.
Our studies have evaluated biochemical changes in placentae from humans exposed to rice oil contaminated with polychlorinated biphenyls (PCBs) and polychlorinated dibenzofurans (PCDFs) in Taiwan. Placentae were obtained from nonsmoking women 4 to 5 years after the exposure had occurred. The exposed individuals ingested approximately 1 to 3 g PCBs and 5 mg PCDFs, and many exhibited symptoms characteristic of PCB poisoning. This disease was termed "Yu-Cheng" in Chinese. Based on data from experimental animal models, we examined a number of parameters in placentae from control and exposed women, including arylhydrocarbon hydroxylase (AHH) activity, cytochrome P-450 isozymes, epidermal growth factor (EGF) receptor binding properties and actions, and Ah receptor. We also quantified concentrations of various PCB and PCDF congeners known to be present in the contaminated rice oil. Our results revealed a dramatic elevation in placental AHH activity in samples from PCB/PCDF-exposed women. This increase in enzyme activity was associated with a parallel increase in placental microsomal protein immunochemically related to cytochrome P-450 form 6 [derived from 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced rabbit lung]. No other cytochrome P-450 isozyme was detected in placental preparations, and the form 6 homolog was found only in placentae from exposed women. EGF receptor-mediated autophosphorylation capacity was significantly diminished in PCB/PCDF placentae, but this effect was not associated with changes in plasma membrane EGF receptor binding properties (Kd and Bmax). The EGF receptor autophosphorylation effect correlated well with the decrease in birthweight observed in offspring of exposed women, suggesting that this biochemical event might provide a good marker of effect for the toxic halogenated aromatics.
Lucier
G W
GW
National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709.
Nelson
K G
KG
Everson
R B
RB
Wong
T K
TK
Philpot
R M
RM
Tiernan
T
T
Taylor
M
M
Sunahara
G I
GI
D000293:Adolescent; D000328:Adult; D001572:Benzofurans / Q000506:poisoning*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D000072338:Dibenzofurans, Polychlorinated; D066246:ErbB Receptors / Q000187:drug effects / Q000378:metabolism; D005260:Female; D005506:Food Contamination; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D012275:Oryza / Q000506:poisoning*; D010920:Placenta / Q000187:drug effects* / Q000378:metabolism; D010938:Plant Oils / Q000506:poisoning*; D011078:Polychlorinated Biphenyls / Q000506:poisoning*; D011247:Pregnancy; D018336:Receptors, Aryl Hydrocarbon; D011955:Receptors, Drug / Q000187:drug effects / Q000378:metabolism
D001572:Benzofurans; D000072338:Dibenzofurans, Polychlorinated; D007527:Isoenzymes; D010938:Plant Oils; D018336:Receptors, Aryl Hydrocarbon; D011955:Receptors, Drug; D003577:Cytochrome P-450 Enzyme System; D011078:Polychlorinated Biphenyls; D066246:ErbB Receptors