Staff Publications

Staff Publications

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    'Staff publications' is the digital repository of Wageningen University & Research

    'Staff publications' contains references to publications authored by Wageningen University staff from 1976 onward.

    Publications authored by the staff of the Research Institutes are available from 1995 onwards.

    Full text documents are added when available. The database is updated daily and currently holds about 240,000 items, of which 72,000 in open access.

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Record number 422791
Title Some OH-PCBs are more potent inhibitors of aromataseactivity and (anti-) glucocorticoids than non-dioxin like (NDL)-PCBs and MeSO2-PCBs
Author(s) Antunes Fernandes, E.C.; Bovee, T.F.H.; Daamen, F.; Helsdingen, J.R.; Berg, M. van den; Duursen, M. van
Source Toxicology Letters 206 (2011)2. - ISSN 0378-4274 - p. 158 - 165.
DOI https://doi.org/10.1016/j.toxlet.2011.07.008
Department(s) Product Design and Quality Management Group
Rikilt B&T Toxicologie en Effectanalyse
Publication type Refereed Article in a scientific journal
Publication year 2011
Keyword(s) methyl sulfone metabolites - adrenocortical carcinoma-cells - brominated flame retardants - polychlorinated-biphenyls - hydroxylated metabolites - methylsulfonyl metabolites - placental-transfer - eastern slovakia - gene-expression - hormone levels
Abstract Traditional risk assessment of potential endocrine-disruptive pollutants, including PCBs, focus mainly on the effects of parent compounds. Still, biotransformation results in systemic exposure to PCBs and their bioactive metabolites. In the present paper, the effects of twenty ultra-pure non-dioxin-like (NDL) PCBs and their environmentally relevant hydroxy- (OH-) and methylsulfonyl- (MeSO2-) metabolites on aromataseactivity and their glucocorticoid properties were investigated. Although most NDL-PCBs were inactive, PCB28 inhibited aromataseactivity in human placenta microsomes with an IC50 of 2.2 µM. Most of these NDL-PCBs were weak (ant-)agonist of the glucocorticoid receptor (GR). Interestingly, four OH-metabolites of the commonly found NDL-PCB180 were able to inhibit aromataseactivity (LOECs in the low µM range) and showed anti-glucocorticoid properties (LOECs in the low nM range), in a concentration-dependent manner. Further, four MeSO2-PCBs slightly inhibited aromataseactivity and showed anti-glucocorticoid properties. Although, these effects were also associated with cytotoxicity, they were dependent on the position of the MeSO2-group on the biphenyl ring. Our results are the first to show that OH-PCBs are both anti-glucocorticoids and aromataseinhibitors. Taken together, these results for PCBs again support the common idea that risk assessment of the endocrine disruptive potential of PCBs should also include their metabolites. --------------------------------------------------------------------------------
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