Evaluation, validation and application of the H295R system for the analysis of endocrine disrupting effects.

摘要

The continuously growing number of compounds synthetically derived or extracted from natural materials daily discovered, designed or produced in order to satisfy human's necessities has brought along unintended effects that have been of human concern for several decades. It has been clearly established that several of these synthetic and naturally occurring chemical substances in the environment are disrupting the normal functions of the endocrine system and its hormones in humans and wildlife. Despite the wide range of studies that have been conducted in this area, in many cases there is still insufficient data to demonstrate specific associations between environmental exposure and endocrine-mediated adverse effects. The need to evaluate endocrine disruption exerted by pathways other than receptor-mediated mechanisms has driven scientists to intensively work in the development of new, practical and more comprehensive bioassays in order to match up the growing speed of chemical design/production. In this dissertation the evaluation, validation and application of the new developed H295R cell bioassay for the evaluation of potential effects of environmental contaminants as endocrine disrupters, was conducted. Results from the executed studies corroborate the versatility of the H295R cell bioassay to identify the different effects of chemicals on steroid production and to point through the different{09}molecular and enzymatic mechanisms that may be responsible for such effects. This method is applicable to any environmental contaminants identified up to the present time, including complex mixtures of them. Moreover, the effectiveness shown in identifying the potential endocrine effects of realistic environmental samples of different matrices is without doubt one of its most valuables applications.