2003 Volume 49 Issue 1 Pages 65-71
Atrazine (2-chloro-4-ethylamino-6-isopropylamino-s-chlorotriazine), one of the most widely used herbicides, is classified as a possible human carcinogen by the US Environmental Protection Agency and is a known endocrine disruptor. Recent research has indicated that the estrogenic and antiestrogenic effects elicited by this chemical are not mediated by the estrogen receptor. In this study, we also observed that not only atrazine but also its metabolites did not affect basal or 17β-estradiol induced MCF7-BUS cell proliferation. Therefore, to explain the apparent endocrine disrupting effects of atrazine in vivo, an estrogen-independent mechanism and its metabolites were studied. We examined the alteration in aromatase (CYP19) activity in human choriocarcinoma JEG-3 cells by atrazine and its major metabolites (hydroxyatrazine, diaminochlorotriazine), the conversion of estradiol to hydroxylated metabolites by these compounds associated with cytochrome P4501A. The common metabolite of atrazine, diaminochlorotriazine inhibited the aromatase activity responsible for estrogen synthesis in JEG-3 cells. Atrazine and its metabolites induced 7-ethoxyresorufin-O-deethylase activity and catalyzed estrogen metabolism in MCF-7 cells. These results suggest that the antiestrogenic effects of atrazine may relate to a decrement in estrogen levels caused by aromatase inhibition and estrogen metabolism stimulation by atrazine and its metabolites.
