Placental markers of human exposure to polychlorinated biphenyls and polychlorinated dibenzofurans.

Lucier, George W.; Nelson, Kay M.; Everson, RichardB.; Wong, T K; Philpot, Richard M.; Tiernan, T. O.; Taylor, Michael J.; Sunahara, G I

doi:10.1289/ehp.877679

Cited by 61 publications

(13 citation statements)

References 31 publications

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“…Increased placental CYP1A1 activity was reported in women accidentally exposed to high levels of PCBs and PCDFs (6,34). However, the mean placental PCB 153 concentration in these women (Yu-Cheng patients) was about 12-fold greater than that reported here for the Nunavik group (8 ppb vs. 0.64 ± 0.02 ppb when converted to wet weight) (34).…”

Section: Discussioncontrasting

confidence: 68%

“…Placental CYP1A1 activity (AHH) in Taiwanese women with Yu-Cheng syndrome was also about 10-fold higher than in American women exposed to background levels of organochlorines who smoked during pregnancy (6). In addition, an inverse correlation of ethoxyresorufin-O-deethylase (EROD) and AHH enzyme activities to birth weight was subsequently reported in Yu-Cheng patients (34). These results indicated that accidental exposure to PCBs and PCDFs induced placental CYP1A1 activity and further suggested a relation between placental CYP1A1 activity and adverse developmental effects.…”

mentioning

confidence: 97%

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Environmental exposure to polychlorinated biphenyls and placental CYP1A1 activity in Inuit women from northern Québec.

Pereg

Dewailly

Poirier

et al. 2002

Environ Health Perspect

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Some polychlorinated biphenyl (PCB) congeners are CYP1A1 inducers, and induction of this enzyme in the placenta has been linked to adverse effects on fetal development. The objective of this study was to determine if the body burden of PCBs is related to placental CYP1A1 activity in Inuit women from Nunavik (northern Québec), a population highly exposed to organochlorines. Placenta and cord blood samples were obtained from 35 Inuit women and 30 women from a southern Québec community exposed to background levels of organochlorines. We measured PCB concentrations in all cord plasma samples and in a subset of placenta samples from the Nunavik group and assessed CYP1A1 activity (ethoxyresorufin-O-deethylase; EROD) in placental microsomes from all participants. Concentrations of PCBs in cord plasma were strongly correlated to those in placenta (Pearson's r) = 0.77-0.97, p < 0.001) and were on average 4-fold higher in Inuit women than in southern Québec women [for PCB 153, the geometric means (geometric SDs) were 83.3 (1.9) ng/g lipid vs. 16.9 (1.6) ng/g lipid, respectively]. Despite this difference in PCB body burden, both study groups had similar EROD activities when data were stratified according to tobacco smoking. Although simple correlation analysis first showed that placental EROD activity was correlated with PCB 153 plasma concentration in the Nunavik group, a multivariate analysis failed to demonstrate a significant contribution of PCBs to EROD activity when tobacco smoking was included in the analysis. We conclude that dietary exposure to PCBs in Inuit women from Nunavik does not significantly influence EROD activity in the placenta, implicating tobacco smoking as the major modulating factor.

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Section: Discussioncontrasting

confidence: 68%

mentioning

confidence: 97%

Environmental exposure to polychlorinated biphenyls and placental CYP1A1 activity in Inuit women from northern Québec.

Pereg

Dewailly

Poirier

et al. 2002

Environ Health Perspect

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“…Lagueux et al (1999) found that CYP1A1 activity was elevated in the placental tissue of Inuit women living in northern Quebec who are exposed to PCBs and other organochlorine compounds from the consumption of marine mammals. Similarly, Lucier et al (1987) reported that Yu-Cheng women exposed to PCBs and dibenzofurans had higher levels of placental CYP1A1 activity than an unexposed control group, and that such activity was inversely correlated with the birth weight of their offspring.…”

Section: Discussionmentioning

confidence: 94%

PCB Exposure and in Vivo CYP1A2 Activity among Native Americans

Fitzgerald

Hwang

Lambert

et al. 2005

Environ Health Perspect

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Cytochrome P-450 1A2 (CYP1A2) is an enzyme involved in the metabolic activation of some carcinogens and is believed to be induced by xenobiotics. Very few studies, however, have investigated the association between environmental exposures and in vivo CYP1A2 activity in humans. To address this issue, a study was conducted of CYP1A2 activity among Native Americans exposed to polychlorinated biphenyls (PCBs) from the consumption of fish from the St. Lawrence River. At the Mohawk Nation at Akwesasne (in New York and in Ontario and Quebec, Canada), 103 adults were interviewed, and they donated blood for serum PCB analysis and underwent the caffeine breath test (CBT), a safe and noninvasive procedure that uses caffeine as a probe for CYP1A2 activity in vivo. The results supported the findings of other studies that CBT values are higher among smokers and men and lower among women who use oral contraceptives. Despite a relatively low average total PCB body burden in this population, the sum of serum levels for nine mono- or di-ortho-substituted PCB congeners showed positive associations with CBT values (p = 0.052 wet weight and p = 0.029 lipid adjusted), as did toxic equivalent quantities (TEQs; p = 0.091 for wet weight and 0.048 for lipid adjusted). Regarding individual congeners, serum levels of PCB-153, PCB-170, and PCB-180 were significantly correlated with CBT values. The results support the notion that CYP1A2 activity may be a marker of an early biological effect of exposure to PCBs in humans and that the CBT may be a useful tool to monitor such effects.

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“…Placentas from women exposed to contaminated rice oil were analyzed for EGF receptor binding and EGF-stimulated autophosphorylation as well as for CYPlA1 activity; the data are displayed in Table 2 (18,19). These compounds are structurally similar to TCDD and are thought to share the same mechanism of action: binding to the Ah receptor and induction of pleiotropic responses.…”

Section: Human Exposuresmentioning

confidence: 99%

Integrated Approach for Evaluating Species and Interindividual Differences in Responsiveness to Dioxins and Structural Analogs

Clark¹,

Tritscher²,

Bell³

et al. 1992

Environmental Health Perspectives

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2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a ubiquitous environmental contaminant that is produced inadvertently during the synthesis of some organochlorine compounds, such as the chlorinated phenoxy pesticides. It is biologically and ecologically persistent, with an estimated half-life of 7 years in humans. It possesses high acute toxicity in rodents and is a carcinogen, teratogen, and immunotoxin. In chronic bioassays for carcinogenicity, TCDD at a dose of 10 ng/kg/day increases the incidence of liver tumors in female rats, making it one of the most potent animal carcinogens ever tested. A recent study in humans has shown an increase in the incidence of respiratory tract tumors in workers in chlorinated phenoxy herbicide plants. Considerable controversy and uncertainty remain, however, concerning its carcinogenic potency in humans and the reliability of using animal data to predict human risks. It is generally accepted that most, if not all, of the effects of TCDD require its binding to the Ah receptor. In addition to its toxic effects, TCDD produces a number of biochemical effects, such as induction of CYPlAl, downregulation ofbinding activity of the estrogen and epidermal growth factor (EGF) receptors, and changes in cytokine pathways. These effects suggest that the Ah receptor plays an important role in regulating the cell cycle. A number of structural analogs of TCDD, such as the polychlorinated dibenzofurans, also interact with the Ah receptor, and they produce the same spectrum of responses as TCDD in animal and cell models. The potency of these compounds is strongly correlated with their binding affinity to the Ah receptor. Perhaps the most sensitive marker of exposure to TCDD in both rodents and humans is induction of a specific isozyme of cytochrome P450 (CYPLA1). Our data suggest that humans are at least as sensitive as rats to CYPIAl enzyme induction (produced by transcriptional activation of the CYPJAI gene) and to down-regulation of the EGF receptor. This conclusion is based on data obtained in vivo (accidentally exposed humans and rats subjected to a two-stage model of hepatocarcinogenesis) and in vitro (incubation of human and rodent lymphocytes with TCDD). There is considerable interindividual variation in human responses to TCDD. Our work on "markers of susceptibility" suggests that both variation in the amount ofAh receptor and a mutation in the CYPLAI gene may be responsible for this variation. Since TCDD gives negative results in short-term tests for genotoxicity and does not bind covalently to DNA, it can be considered a prototypical chemical for the study of receptor-mediated carcinogenesis

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Placental markers of human exposure to polychlorinated biphenyls and polychlorinated dibenzofurans.

Cited by 61 publications

References 31 publications

Environmental exposure to polychlorinated biphenyls and placental CYP1A1 activity in Inuit women from northern Québec.

Environmental exposure to polychlorinated biphenyls and placental CYP1A1 activity in Inuit women from northern Québec.

PCB Exposure and in Vivo CYP1A2 Activity among Native Americans

Integrated Approach for Evaluating Species and Interindividual Differences in Responsiveness to Dioxins and Structural Analogs

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