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 investigated in vivo using the immature female Sprague-Dawley rat uterus and in vitro using the estrogen-responsive MCF-7 human breast cancer cell line and the estrogen-dependent recombinant yeast strain PL3. Animals 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 receptor (PR) binding levels and uterine peroxidase activity were observed. 17 beta-estradiol (E2)-induced increases in uterine wet weight were not significantly affected by cotreatment with either chemical; however, some dose-independent decreases in E2-induced cytosolic PR binding and uterine peroxidase activity were observed. In vitro, atrazine and simazine did not affect basal or E2-induced MCF-7 cell proliferation or the formation of nuclear PR-DNA complexes as determined by gel electrophoretic 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 estrogen receptor chimera (Gal4-HEGO) and a Gal4-regulated luciferase reporter gene (17m5-G-Luc). Moreover, the estrogen-dependent PL3 yeast strain was not capable of growth on minimal media supplemented with atrazine or simazine in place of E2. Collectively, these results indicate that the reported estrogenic and antiestrogenic effects elicited by these chemicals are not mediated by the estrogen receptor.
Connor
K
K
Department of Veterinary Physiology and Pharmacology, Texas A&M University, College Station 77843-4466, USA.
Howell
J
J
Chen
I
I
Liu
H
H
Berhane
K
K
Sciarretta
C
C
Safe
S
S
Zacharewski
T
T
D000818:Animals; D001280:Atrazine / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D005260:Female; D017930:Genes, Reporter / Q000187:drug effects; D009195:Peroxidase / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D011960:Receptors, Estrogen / Q000037:antagonists & inhibitors / Q000187:drug effects*; D011980:Receptors, Progesterone / Q000187:drug effects; D012839:Simazine / Q000494:pharmacology*; D014599:Uterus / Q000187:drug effects* / Q000201:enzymology
D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D009195:Peroxidase; D001280:Atrazine; D012839:Simazine