PARENT SESSION

2L (1) - Immunotoxicity - genotoxicity - ED
Hall 8
8:30 AM - 10:15 AM, Wednesday, 30 April 2003
Chair: Hansen, P.D.¹, ¹

(TH8/2) Why do degradation products of alkylphenolpolyethoxylates cause anti-estrogenic effects?

Rutishauser, Barbara¹, Eggen, Rik¹, ¹ Swiss Federal Institute for Environmental Science and Technology (EAWAG), Dübendorf, Switzerland

ABSTRACT- In vitro assays for the detection of estrogenic activity are widely used as screening tools. Frequently used assays are the yeast estrogen screens (YES; e.g. Routledge E.J. and Sumpter J.P. Environ. Toxicol. Chem. 15 (3): 241-248, 1996). The YES turned out to be reliable and robust tools but for some observations like inhibitory effects of samples there are no or only poor explanations available on a mechanistic level. Starting from the finding that nonylphenoxy acetic acid (NP1EC) and octylphenoxy acetic acid (OP1EC), degradation products of the corresponding alkylphenolpolyethoxylates, are showing anti-estrogenic effects in a YES, investigations into possible mechanisms were undertaken. Uptake of estradiol was not influenced by the presence of NP1EC. Receptor binding studies revealed that both NP1EC and OP1EC were capable of binding to the human estrogen receptor (hER ). Further investigations were carried out to find out why after the binding to the receptor transcription of the reporter gene in the YES is not induced as this is the case for nonylphenol (NP), the final degradation product of nonylphenolpolyethoxylates. NP1EC, which was taken as representative, induced conformational changes upon binding to the receptor which were different from the ones induced by E2 and also different than those induced after the binding of NP. Gel mobility shift assays indicated that the hER after binding of NP1EC was no longer able to bind a consensus estrogen responsive element (ERE). This lack of binding after displacement of E2 from the receptor is suggested as explanation for the anti-estrogenic activity of NP1EC in the YES.

Key words: yeast estrogen screen, anti-estrogenic effects, alkylphenoxy acetic acids, mechanistic level