2 COMPLEMENTARY BIOASSAYS FOR SCREENING THE ESTROGENIC POTENCY OF XENOBIOTICS - RECOMBINANT YEAST FOR TROUT ESTROGEN-RECEPTOR AND TROUT HEPATOCYTE CULTURES

A relation between the chemical structure of a xenobiotic and its ster oidal action has not yet been clearly established. Thus, it is not pos sible to define the estrogenic potency of different xenobiotics. An as sessment may be accomplished by the use of different bioassays. We hav e previously developed a yeast system highly and stably expressing rai nbow trout estrogen receptor (rtER) in order to analyze the biological activity of the receptor. The recombinant yeast system appears to be a reliable, rapid and sensitive bioassay for the screening and determi nation of the direct interaction between ER and estrogenic compounds. This system was used in parallel with a more elaborate biological syst em, trout hepatocyte aggregate cultures, to examine the estrogenic pot ency of a wide spectrum of chemicals commonly found in the environment . In hepatocyte cultures, the vitellogenin gene whose expression is pr incipally dependent upon estradiol was used as a biomarker. Moreover, competitive binding assays were performed to determine direct interact ion between rtER and xenobiotics. In our study, 50% of the 49 chemical compounds tested exhibited estrogenic activity in the two bioassays: the herbicide diclofop-methyl; the fungicides biphenyl, dodemorph, and triadimefon; the insecticides lindane, methyl parathion, chlordecone, dieldrin, and endosulfan; polychlorinated biphenyl mixtures; the plas ticizers or detergents alkylphenols and phthalates; and phytoestrogens . To investigate further biphenyl estrogenic activity, its principal m etabolites were also tested in both bioassays. Among these estrogenic compounds, 70% were able to activate rtER in yeast and hepatocytes wit h variable induction levels according to the system. Nevertheless, 30% of these estrogenic compounds exhibited estrogenic activity in only o ne of the bioassays, suggesting the implication of metabolites or diff erent pathways in the activation of gene transcription. This paper sho ws that it is important to combine in vivo bioassays with in vitro app roaches to elucidate the mechanism of xenoestrogen actions.