Impact of peri-urban landscape on the organic and mineral contamination of pond waters and related risk assessment.

Ponds are important for their ecological value and for the ecosystem services they provide to human societies, but they are strongly affected by human activities. Peri-urban development, currently one of the most pervasive processes of land use change in Europe, exposes ponds to both urban and agricultural contaminants, causing a potential combination of adverse effects. This study, focused on 12 ponds located in a peri-urban area, has two main objectives: (1) to link the physico-chemical characteristics of the waters and the nature of their contaminants, either organic or mineral, with the human activities around ponds, and (2) to estimate the environmental risk caused by these contaminants. The ponds were sampled during two consecutive years in both spring and in autumn. Although the ponds were distributed over a limited geographical area, their contamination profiles were different and more correlated with the agricultural than the urban land use. In terms of aptitude for biology, half of the ponds were classified in degraded states due to their physico-chemical parameters, but without correlation with the endocrine disrupting activities and the levels of organic pollutants as indicators. The main quantified organic pollutants, however, were pesticides with sufficiently high levels in certain cases to induce an environmental risk exceeding the classical thresholds of risk quotient.

First characterization of the endocrine-disrupting potential of indoor gaseous and particulate contamination: comparison with urban outdoor air (France).

The composition of endocrine-disrupting compounds (EDCs) in the ambient air of indoor environments has already been described, but little is known about the inherent endocrine-disrupting potential of indoor air contamination. We therefore aimed to study the distribution of bioactive EDCs in the gaseous and particulate phases of indoor air using a cellular bioassay approach that integrates the interaction effects between chemicals. Organic air extracts, both gaseous and particulate, were taken from three indoor locations (office, apartment, and children's day care) in France and sampled in two different seasons in order to study their interference with the signaling of estrogen, androgen, and thyroid receptors. The experiments were also conducted on aerial extracts from an outdoor site (urban center). We found that gaseous and/or particulate extracts from all locations displayed estrogenicity, anti-androgenicity, and thyroidicity. Overall, indoor air extracts had a higher endocrine-disrupting potential compared to outdoor ones, especially during winter and in the day care. The biological activities were predominant for the gaseous extracts and tended to increase for the particulate extracts in cool conditions. In conclusion, our data confirmed the presence of bioactive EDCs in a gaseous state and highlighted their indoor origin and concentration, especially in the cold season.

Xenoestrogens modulate genotoxic (UVB)-induced cellular responses in estrogen receptors positive human breast cancer cells.

Human populations and wildlife are exposed to mixtures of both anthropogenic and natural chemicals. Some of these compounds are known to interact principally with the endocrine function, whereas others act mainly on genomic DNA. Given this evidence, we wanted to address the question of whether concomitant exposure of such chemicals was able to interact at the cellular level. We have previously shown that 17ß-Estradiol (E(2)) modulates the DNA repair capacity of cells. In this work, we wanted to examine if other xenoestrogens (i.e. industrial compounds, pesticides or pharmaceuticals) were able to interact with the UVB-induced cellular response as E(2) does. Here, we show that xenoestrogens modulate the capacity of cells to repair their DNA damage according to the type of compounds. For example, the oral contraceptive 17α-Ethinylestradiol down-regulated the repair of UVB-induced DNA damage whereas the UV filter Eusolex 6007 up-regulated this pathway. The notion that xenoestrogens could interact with a genotoxic stress is reinforced by the modulation of the estrogens-dependent luciferase reporter gene expression when cells are UVB-irradiated. Finally, these observations suggested the potential role of xenoestrogens in carcinogenesis by their capacity to modulate cells responses to genotoxic stress.

Tetrabromobisphenol-A disrupts thyroid hormone receptor alpha function in vitro: use of fluorescence polarization to assay corepressor and coactivator peptide binding.

Thyroid hormone receptors (TRs) recruit corepressor or coactivator factors to the promoters of target genes to regulate their transcription. Corepressors such as nuclear hormone receptor corepressor (NCoR) are recruited by unliganded TRs, whereas coactivators such as steroid receptor coactivator-2 (SRC2) are recruited when triiodothyronine (T3) is bound to TRs. These coregulator proteins interact with the ligand binding domain (LBD) of TRs via short, conserved peptide sequences that can be used to probe the conformational changes induced in TR LBD by TR ligands. Recombinant LBD of the human TRα1 isoform (hTRα1 LBD) was produced as a fusion with glutathione S-transferase, and used to develop assays based on fluorescence polarization to quantify the binding of either NCoR- or SRC2-derived fluorescent peptides to the hTRα1 LBD. The optimum concentrations of recombinant hTRα1 LBD, and of peptide probes were adjusted in order to produce the greatest possible T3-dependent signal variations in fluorescence polarization. Under these conditions, T3 induced a dose-dependent decrease in NCoR peptide binding, and a reciprocal dose-dependent increase in SRC2 peptide binding, in both cases at similar 50%-effective doses. The TR agonists triiodothyroacetic acid and thyroxine were also effective in preventing NCoR peptide binding and increasing SRC2 peptide binding, whereas reverse-triiodothyronine was less efficient and the biologically inactive thyronine had no effect on either process. These experiments validate cell-free assays based on the use of binding of corepressor or coactivator peptide probes, as measured by fluorescence polarization, for investigating the conformational changes of TRα1 LBD induced by potentially TR-interfering compounds. Both these methods were used to elucidate the mechanism of the disrupting effects of tetrabromobisphenol-A (TBBPA) on the hTRα1 LBD conformation related to the transcriptional activity of the receptor. TBBPA is a flame retardant that is released into the environment, and is a suspected disrupter of thyroid homeostasis. The present results indicate that TBBPA did indeed interfere with the ability of the hTRα1 LBD to bind both NCoR and SRC2. TBBPA behaved similarly to T3 in promoting the release of NCoR from LBD, whereas it failed to promote LBD interactions with SRC2. However, it did reduce the T3-induced interactions between LBD and the coactivator peptide. This study therefore suggests that TBBPA in the micromolar range can affect the regulation of transcription by both the apo- and the holo-TRα1, with potential disruption of the expression of genes that are either up- or down-regulated by T3.