Antiestrogenic Activity of Hydroxylated Polychlorinated Biphenyl Congeners Identified in Human Serum

Moore, Michael J.; Mustain, M.; Daniel, K; Chen, I; Safe, Stephen; Zacharewski, Tim; Gillesby, Bradley E.; Joyeux, Annick; Balaguer, Patrick

doi:10.1006/taap.1996.8022

Cited by 150 publications

(80 citation statements)

References 2 publications

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“…4-OH-CB107 is known to exert anti-estrogenicity in vitro (Moore et al, 1997;Meerts, unpublished results). High concentrations of this metabolite in the developing brain may influence CNS dopaminergic and serotonergic function, as there appear to exist interactive relationships between estrogens and DA as well as between estrogens and 5-HT (Rubinow et al, 1998;reviewed in McEwen and Alves, 1999).…”

Section: Discussionmentioning

confidence: 96%

Developmental Exposure to 4-hydroxy-2,3,3',4',5-pentachlorobiphenyl (4-OH-CB107): Long-Term Effects on Brain Development, Behavior, and Brain Stem Auditory Evoked Potentials in Rats

Meerts

Lilienthal²,

Hoving³

et al. 2004

Toxicological Sciences

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In the present study the developmental neurotoxic effects of the PCB metabolite 4-OH-2,3,3 0 ,4 0 ,5-pentachlorobiphenyl (4-OH-CB107) were compared with effects caused by a mixture of parent polychlorinated biphenyl (PCB) congeners (Aroclor 1254). Pregnant female Wistar rats were exposed to 0.5 or 5 mg 4-OH-CB107, or 25 mg Aroclor 1254 per kg body weight from gestation days 10 to 16. Plasma thyroid hormone levels were significantly decreased in the offspring of all treatment groups at postnatal day 4 (PND 4). Behavioral experiments using an open field paradigm revealed an impaired habituation in male offspring of all treatment groups at PND 130. Passive avoidance experiments indicated significant influences on the time course of step-down latencies across trials in exposed male rats. Catalepsy induced by haloperidol showed increases in latencies to movement onset in female offspring exposed to 0.5 mg 4-OH-CB107 compared to Aroclor 1254 treated offspring at PND 168-175. Male offspring exposed to 4-OH-CB107 or Aroclor 1254 showed decreases in latencies compared to control animals. Brain stem auditory evoked potentials (BAEPs) measured at PND 300-310 showed significant increases in auditory thresholds in the low frequency range between Aroclor 1254 and 4-OH-CB107 (5 mg/kg bw) treated animals. Measurements of neurotransmitter levels revealed effects of Aroclor 154 exposure on both the dopaminergic and the serotonergic systems, whereas 4-OH-CB107 exposure affected dopaminergic and noradrenergic systems, with slight but not significant effects on the serotonergic system. These results indicate that 4-OH-CB107 is able to induce long-term effects on behavior and neurodevelopment. The observed effects for 4-OH-CB107 are similar to, but in some aspects different from, the effects observed after Aroclor 1254 exposure.

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Section: Discussionmentioning

confidence: 96%

Developmental Exposure to 4-hydroxy-2,3,3',4',5-pentachlorobiphenyl (4-OH-CB107): Long-Term Effects on Brain Development, Behavior, and Brain Stem Auditory Evoked Potentials in Rats

Meerts

Lilienthal²,

Hoving³

et al. 2004

Toxicological Sciences

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“…A number of OHPCBs identified in human serum exhibited antiestrogenic activity in the rat uterine estrogen-binding assay and in the MCF-7 cell proliferation assay (9). OH-PCBs bound to the estrogen receptor and transactivated the estrogen receptor to DNA binding and altered gene expression in in vitro reporter gene assays (9,10 (17). PCB mixtures are also capable of inducing T4 glucuronidation (18)(19)(20)(21).…”

Section: Estrogen Receptor-mediated Effectsmentioning

confidence: 99%

Characterization of Potential Endocrine-Related Health Effects at Low-Dose Levels of Exposure to PCBs

Brouwer¹,

Longnecker²,

Birnbaum³

et al. 1999

Environmental Health Perspectives

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This article addresses issues related to the characterization of endocrine-related health effects resulting from low-level exposures to polychlorinated biphenyls (PCBs). It is not intended to be a comprehensive review of the literature but reflects workshop discussions. "The Characterizing the Effects of Endocrine Disruptors on Human Health at Environmental Exposure Levels," workshop provided a forum to discuss the methods and data needed to improve risk assessments of endocrine disruptors. This article contains an overview of endocrine-related (estrogen and thyroid system) interactions and other low-dose effects of PCBs. The data set on endocrine effects includes results obtained from mechanistic methods/ and models (receptor based, metabolism based, and transport protein based), as well as from in vivo models, including studies with experimental animals and wildlife species. Other low-dose effects induced by PCBs, such as neurodevelopmental and reproductive effects and endocrine-sensitive tumors, have been evaluated with respect to a possible causative linkage with PCB-induced alterations in endocrine systems. In addition, studies of low-dose exposure and effects in human populations are presented and critically evaluated. A list of conclusions and recommendations is included.

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“…To demonstrate a specific interaction between chemicals and ER, an assay with a chimeric receptor molecule has been developed 42,[45][46][47] , in which the C-terminal liganddependent activation domain of ER is fused to the DNA binding domain of yeast transcription factor GAL4. This artificial chimeric receptor molecule retains the ligandspecificity, and it can give rise to transactivation via the GAL4 binding sequence located upstream of the reporter gene.…”

Section: Other Applicationsmentioning

confidence: 99%

Gene Expression Assay for Hazard Assessment of Chemicals.

Otsuka

2002

INDUSTRIAL HEALTH

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Recent progress in our knowledge of gene expression systems provides evidence that many industrial chemicals affect the transcriptional machineries directly or indirectly, and gene expression is now recognized as one of the main targets of many chemicals. In view of the increasing number of man-made chemicals, it is therefore necessary to establish a reliable gene expression assay with rapidity and high sensitivity. Among various gene expression assays, the so-called reporter assay is now accepted as a suitable tool to assess hazardous effects of chemicals on gene expression. This article focuses on the principle and applications of the reporter assay in research on endocrine disrupters.

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Antiestrogenic Activity of Hydroxylated Polychlorinated Biphenyl Congeners Identified in Human Serum

Cited by 150 publications

References 2 publications

Developmental Exposure to 4-hydroxy-2,3,3',4',5-pentachlorobiphenyl (4-OH-CB107): Long-Term Effects on Brain Development, Behavior, and Brain Stem Auditory Evoked Potentials in Rats

Developmental Exposure to 4-hydroxy-2,3,3',4',5-pentachlorobiphenyl (4-OH-CB107): Long-Term Effects on Brain Development, Behavior, and Brain Stem Auditory Evoked Potentials in Rats

Characterization of Potential Endocrine-Related Health Effects at Low-Dose Levels of Exposure to PCBs

Gene Expression Assay for Hazard Assessment of Chemicals.

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