various uterine responses in female Sprague-Dawley and Failure of Chloro-S-triazine-Derived Compounds to Induce Es-Fischer 344 rats (Eldridge et al., 1994;Stevens et al., 1994; trogen Receptor-Mediated Responses in Vivo and in Vitro. CON- Tennant et al., 1994a,b;Wetzel et al., 1994). These studies NOR, K., HOWELL, J., CHEN, I., LIU, H., BERHANE, K., SCIAR-found that atrazine and simazine may inhibit 17b-estradiol tremely high doses. For example, chronic feeding of high The potential estrogenic activities of atrazine and simazine were dietary levels of atrazine increased the number of days in investigated in vivo using the immature female Sprague-Dawley estrus and hastened the onset but not the incidence of mamrat uterus and in vitro using the estrogen-responsive MCF-7 hu-mary tumors in female Sprague-Dawley rats. In contrast, man breast cancer cell line and the estrogen-dependent recombi-these changes were not observed in female Fischer 344 rats; nant yeast strain PL3. Animals that were dosed with 50, 150, or these animals exhibited a significantly lower incidence of 300 mg/kg of atrazine or simazine alone for 3 consecutive days spontaneous age-dependent mammary tumors than observed did not exhibit any significant increases in uterine wet weight while in Sprague-Dawley rats. There is also evidence suggesting decreases in cytosolic progesterone receptor (PR) binding levels that these chloro-S-triazines decrease rat uterine estrogen and uterine peroxidase activity were observed. 17b-estradiol (E2)-receptor (ER) binding and uterine wet weights. Moreover, induced increases in uterine wet weight were not significantly affected by cotreatment with either chemical; however, some dose-rats that were treated with E2 plus simazine or atrazine expeindependent decreases in E2-induced cytosolic PR binding and rienced a decrease in E2-induced progesterone receptor (PR) uterine peroxidase activity were observed. In vitro, atrazine and binding and DNA synthesis (Tennant et al., 1994b). Taken simazine did not affect basal or E2-induced MCF-7 cell prolifera-together, these results suggest that atrazine and simazine tion or the formation of nuclear PR-DNA complexes as deter-may possess estrogenic and/or antiestrogenic activities that mined by gel electrophoretic mobility shift assays. In addition, are mediated by the ER.
these chloro-S-triazines did not display agonist activity or antago-Recently, Tennant and co-workers reported that atrazine nize E2-induced luciferase activity in MCF-7 cells transiently and simazine did not effectively displace [ 3 H]E2 from the transfected with a Gal4-human estrogen receptor chimera (Gal4-rat uterine cytosolic ER (Tennant et al., 1994b). Data from HEGO) and a Gal4-regulated luciferase reporter gene (17m5-GLuc). Moreover, the estrogen-dependent PL3 yeast strain was not competitive displacement assays indicate that k i values for capable of growth on minimal media supplemented with atrazine these chloro-S-triazines ranged from 10 to 100 mM and that or simazine in place of E2. Collectively, these ...