RESUMEN
Environmental chemicals with estrogenic activities have been suggested to be associated with deleterious effects in animals and humans. To characterize estrogenic chemicals and their mechanisms of action, we established in vitro and cell culture assays that detect human estrogen receptor [alpha] (hER[alpha])-mediated estrogenicity. First, we assayed chemicals to determine their ability to modulate direct interaction between the hER[alpha] and the steroid receptor coactivator-1 (SRC-1) and in a competition binding assay to displace 17ss-estradiol (E(2)). Second, we tested the chemicals for estrogen-associated transcriptional activity in the yeast estrogen screen and in the estrogen-responsive MCF-7 human breast cancer cell line. The chemicals investigated in this study were o,p'-DDT (racemic mixture and enantiomers), nonylphenol mixture (NPm), and two poorly analyzed compounds in the environment, namely, tris-4-(chlorophenyl)methane (Tris-H) and tris-4-(chlorophenyl)methanol (Tris-OH). In both yeast and MCF-7 cells, we determined estrogenic activity via the estrogen receptor (ER) for o,p'-DDT, NPm, and for the very first time, Tris-H and Tris-OH. However, unlike estrogens, none of these xenobiotics seemed to be able to induce ER/SRC-1 interactions, most likely because the conformation of the activated receptor would not allow direct contacts with this coactivator. However, these compounds were able to inhibit [(3)H]-E(2) binding to hER, which reveals a direct interaction with the receptor. In conclusion, the test compounds are estrogen mimics, but their molecular mechanism of action appears to be different from that of the natural hormone as revealed by the receptor/coactivator interaction analysis.
Asunto(s)
Contaminantes Ambientales/toxicidad , Receptores de Estrógenos/efectos de los fármacos , Factores de Transcripción/efectos de los fármacos , Xenobióticos/toxicidad , Neoplasias de la Mama/patología , Técnicas de Cultivo de Célula/métodos , Femenino , Histona Acetiltransferasas , Humanos , Coactivador 1 de Receptor Nuclear , Receptores de Estrógenos/fisiología , Pruebas de Toxicidad/métodos , Factores de Transcripción/fisiología , Activación Transcripcional , LevadurasRESUMEN
Estimation of time of death (TOD) of white-tailed deer is important to wildlife law enforcement officers. The purpose of this study was to develop and test a model for estimating TOD of white-tailed deer in Missouri. We compare the utility of carcass temperature, pupil diameter, and rigor mortis as TOD indicators. The effects of body size, ambient temperature, and various carcass handling methods on the estimate were also examined. Data were collected from 1484 deer during the 1995-96 and 1996-97 hunting seasons. Stepwise regression indicated that all three indicators were significant and that body size and ambient temperature could influence the model. Predictive equations were developed for various combinations of the indicators based on practicality and statistical probabilities. TOD was estimated for 28 animals where the exact TOD was known. There was no significant difference between the estimated and known TOD (p = 0.759) and the average of the absolute differences in 1 h and 28 min.