THE E-SCREEN ASSAY AS A TOOL TO IDENTIFY ESTROGENS - AN UPDATE ON ESTROGENIC ENVIRONMENTAL-POLLUTANTS

Estrogens are defined by their ability to induce the proliferation of cells of the female genital tract. The wide chemical diversity of estr ogenic compounds precludes an accurate prediction of estrogenic activi ty on the basis of chemical structure. Rodent bioassays are not suited for the large-scale screening of chemicals before their release into the environment because of their cost, complexity, and ethical concern s. The E-SCREEN assay was developed to assess the estrogenicity of env ironmental chemicals using the proliferative effect of estrogens on th eir target cells as an end point. This quantitative assay compares the cell number achieved by similar inocula of MCF-7 cells in the absence of estrogens (negative control) and in the presence of 17 beta-estrad iol (positive control) and a range of concentrations of chemicals susp ected to be estrogenic. Among the compounds tested, several ''new'' es trogens were found; alkylphenols, phthalates, some PCB congeners and h ydroxylated PCBs, and the insecticides dieldrin, endosulfan, and toxap hene were estrogenic by the E-SCREEN assay. In addition, these compoun ds competed with estradiol for binding to the estrogen receptor and in creased the levels of progesterone receptor and pS2 in MCF-7 cells, as expected from estrogen mimics. Recombinant human growth factors (bFGF , EGF, IGF-1) and insulin did not increase cell yields. The aims of th e work summarized in this paper were a) to validate the E-SCREEN assay ; b) to screen a variety of chemicals present in the environment to id entify those that may be causing reproductive effects in wildlife and humans; c) to assess whether environmental estrogens may act cumulativ ely; and finally d) to discuss the reliability of this and other assay s to screen chemicals for their estrogenicity before they are released into the environment.