FAILURE OF CHLORO-S-TRIAZINE-DERIVED COMPOUNDS TO INDUCE ESTROGEN RECEPTOR-MEDIATED RESPONSES IN-VIVO AND IN-VITRO

The potential estrogenic activities of atrazine and simazine were inve stigated in vivo using the immature female Sprague-Dawley rat uterus a nd in vitro using the estrogen-responsive MCF-7 human breast cancer ce ll line and the estrogen-dependent recombinant yeast strain PL3. Anima ls that were dosed with 50, 150, or 300 mg/kg of atrazine or simazine alone for 3 consecutive days did not exhibit any significant increases in uterine wet weight while decreases in cytosolic progesterone recep tor (PR) binding levels and uterine peroxidase activity were observed. 17 beta-estradiol (E2)-induced increases in uterine wet weight were n ot significantly affected by cotreatment with either chemical; however , some dose-independent decreases in E2-induced cytosolic PR binding a nd uterine peroxidase activity were observed, In vitro, atrazine and s imazine did not affect basal or E2-induced MCF-7 cell proliferation or the formation of nuclear PR-DNA complexes as determined by gel electr ophoretic mobility shift assays. In addition, these chloro-S-triazines did not display agonist activity or antagonize E2-induced luciferase activity in MCF-7 cells transiently transfected with a Gal4-human estr ogen receptor chimera (Gal4-HEGO) and a Gal4-regulated luciferase repo rter gene (17m5-G-Luc). Moreover, the estrogen-dependent PL3 yeast str ain was not capable of growth on minimal media supplemented with atraz ine or simazine in place of E2. Collectively, these results indicate t hat the reported estrogenic and antiestrogenic effects elicited by the se chemicals are not mediated by the estrogen receptor. (C) 1996 Socie ty of Toxicology