IGEM:PennState/Labbook/Nimrah Ahmed/2008/05/27

{| width="800"
 * style="background-color: #EEE"|[[Image:owwnotebook_icon.png|128px]] Project name
 * style="background-color: #F2F2F2" align="center"|  |Main project page
 * style="background-color: #F2F2F2" align="center"|  |Main project page


 * colspan="2"|
 * colspan="2"|

Toxicology & PPAR Research

 * 3 PPAR's: PPAR α, β/δ, γ


 * Jeff Peters' page: http://jpeters.vetsci.psu.edu/


 * PPAR inhibits epidermal cell proliferation by down regulating kinase activity http://www.jbc.org/cgi/reprint/280/10/9519

Papers of interest

 * Title: Comparison of the endocrine effects of treated wastewaters from different paper mills by use of an in-vitro test with modified yeast cells.
 * Hamm U, Schabel S, Oeller HJ.
 * Water Sci Technol. 2007;55(6):213-21.
 * As opposed to effluents from chemical pulp production, very little is known about the endocrine potential of papermaking effluents. To evaluate the endocrine potential of biologically treated effluents from the main grades produced in Germany (fine, graphic and packaging papers), 16 samples were studied by means of the Recombinant Yeast Estrogen Assay (R-YEA). 10 samples were tested positive; seven of them were effluents from recovered paper processing mills. Possible sources of endocrine disruptors in addition to wood components include papermaking chemicals, paper converting chemicals, if recovered paper is used, and/or detrimental substances introduced by impurities in these chemicals. Six of the above samples were subjected to individual substance analyses to detect endocrinologically active or potentially endocrinologically active substances. Even though phthalate compounds were detected in concentrations between 0.46 and 2.36 microg/L, only two of the six samples were tested positive in the R-YEA, because the test fails to adequately detect this compound's class. Despite this drawback, the R-YEA will be used for further studies because of the great variety of potential endocrine substances present in paper mill effluents. In particular, mechanical and recycled fibre pulps as well as the constituents of chemical additives must be investigated in more detail.
 * PMID: 17486854 [PubMed - indexed for MEDLINE]


 * Title: The use of in vitro bioassays to quantify endocrine disrupting chemicals in municipal wastewater treatment plant effluents.
 * Nelson J, Bishay F, van Roodselaar A, Ikonomou M, Law FC.
 * Sci Total Environ. 2007 Mar 1;374(1):80-90. Epub 2007 Jan 24.
 * In vitro bioassays are widely used to detect and quantify endocrine disrupting chemicals (EDCs) in the influents and effluents of municipal wastewater treatment plants (WWTP). These assays have sometimes led to false positive or negative results, partly due to the low EDC concentrations in the samples. The objectives of the present study were: (a) to compare the estrogen screen (E-Screen) and the yeast estrogen screen (YES) bioassays using the 17beta-estradiol (E2) or its equivalence and (b) to investigate if a combination of the E-Screen and YES assays can be used to improve the accuracy of EDC detection and quantification. The E-Screen bioassay was conducted with the MCF-7 (BOS) human breast cancer cell line while the YES bioassay employed two different types of recombinant yeast. The influent and effluent samples collected from the five WWTPs operated by the Greater Vancouver Regional District (GVRD) were analyzed by both the E-Screen and the YES bioassays. Since the results of the E-Screen and YES bioassays varied by up to 4-fold on the same split sample of a nominal E2 concentration, the mean value of the E-screen and YES bioassays was used to represent the EDC activity of a given WWTP sample. Results of these studies showed that the E2 equivalent concentration in each WWTP sample was consistently higher than 1 ng/L, a concentration that may potentially cause endocrine disruption in different aquatic species. The composition of selected EDCs in a subset of effluent samples was examined using a gas chromatograph-high resolution mass spectrometer (GC-HRMS). EDC composition in 10 WWTP samples correlated with the mean endocrine disrupting activities of the E-Screen and YES bioassays. Results also indicated that secondary treatment plants are comparable to the primary treatment plants in removing EDCs from the final effluents.
 * PMID: 17257656


 * Keng-Yen Fu, Chung-Yuan Chen, Whei-meih Chang, Application of a yeast estrogen screen in non-biomarker species Varicorhinus barbatulus fish with two estrogen receptor subtypes to assess xenoestrogens, Toxicology in VitroVolume 21, Issue 4,, June 2007, Pages 604-612.
 * (http://www.sciencedirect.com/science/article/B6TCP-4MM1P30-1/1/203a331d9cd16d4b289e6a4c49941c9d)
 * Abstract: Xenoestrogens can interfere with normal estrogen signaling by competitively binding to the estrogen receptor (ER) and activating transcription of target genes. In this study, we cloned the estrogen receptor alpha (vbER[alpha]) and beta 2 (vbER[beta]2) genes from liver of the indigenous Taiwanese cyprinid fish Varicorhinus barbatulus and tested the direct impact of several xenoestrogens on these ERs. Transcriptional activity of xenoestrogens was measured by the enzymatic activity of estrogen responsive element (ERE)-containing [beta]-galactosidase in a yeast reporter system. The xenoestrogens tested were phenol derivatives, DDT-related substances, phthalic acid esters, and polychlorinated biphenyls, with 17[beta]-estradiol (E2) as a subjective standard. The phenol derivatives [4-nonylphenol (4-NP), 4-t-octylphenol (4-t-OP) and bisphenol A (BPA)] exhibited significant dose-dependent responses in both ligand potency and ligand efficiency. Consistent with yeast assays using human or rainbow trout ERs, we observed a general subtype preference in that vbER[alpha] displayed higher relative potencies and efficiencies than vbER[beta]2, although our assays induced a stronger response for xenoestrogens than did human or trout ERs. Whereas 4-NP and 4-t-OP have similar EC50 values relative to E2 for both ER subtypes, the strong estrogenic response of BPA markedly differentiates vbER[alpha] from vbER[beta]2, suggesting possible species-specific BPA sensitivity. We report that the ameliorative yeast tool is readily applicable for indigenous wildlife studies of the bio-toxic influence of xenoestrogens with wildlife-specific estrogen receptors.
 * Keywords: Estrogen receptor; Ligand efficiency; Ligand potency; Transcriptional activation; Xenoestrogen


 * }