caa a22 4500 378861328 CHVBK 20180305123347.0 cr unu---uuuuu 161128e20030101xx s 000 0 eng 10.1351/pac200375112423 doi (NATIONALLICENCE)gruyter-10.1351/pac200375112423 Daston George P. Miami Valley Laboratories, Procter &Gamble, Cincinnati, OH 45253, USA Transcript profiles elicited by developmental exposure to endocrine-mediated toxicants [Elektronische Daten] [George P. Daston] Genomics can be applied in toxicology as a means of identifying modes of action, for generating hypotheses on the relationships of gene activity and toxicity, and for better characterizing the nature of dose-response relationships at low doses. This paper provides examples from our research on endocrine active compounds that illustrate each of these applications. We have determined that agents that bind estrogen receptors produce a characteristic transcript profile in estrogen-responsive tissues of the fetal and juvenile rat. The transcript profile is diagnostic of the mechanism of action. The transcripts that are up- or down-regulated by estrogens belong to a number of functional groups, such as growth factors, pro-apoptotic factors, transcription factors, and steroid metabolizing enzymes. There are a number of testable hypotheses that can be generated from these data regarding the relationships between changes in these genes and developmental or physiological responses to estrogens. We have determined that the sensitivity of gene expression changes is high, making it possible to define the shape of the dose-response curve at dose levels of estrogen several orders of magnitude below those that cause a physiological response (in this case, a uterotrophic response). The shape of the dose response is monotonic: both the number of genes changed and the intensity of the up- or down-regulation decreases with decreasing dose. © 2013 Walter de Gruyter GmbH, Berlin/Boston Pure and Applied Chemistry De Gruyter 75/11-12(2003-01-01), 2423-2427 0033-4545 75:11-12<2423 2003 75 pac https://doi.org/10.1351/pac200375112423 text/html Onlinezugriff via DOI 1 research article jats NATIONALLICENCE 856 40 https://doi.org/10.1351/pac200375112423 text/html Onlinezugriff via DOI NATIONALLICENCE 100 1- Daston George P. Miami Valley Laboratories, Procter &Gamble, Cincinnati, OH 45253, USA NATIONALLICENCE 773 0- Pure and Applied Chemistry De Gruyter 75/11-12(2003-01-01), 2423-2427 0033-4545 75:11-12<2423 2003 75 pac CC0 http://creativecommons.org/publicdomain/zero/1.0 nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-gruyter