Tennant M K, Hill D S, Eldridge J C, Wetzel L T, Breckenridge C B, Stevens J T
Department of Physiology and Pharmacology, Bowman Gray School of Medicine, Wake Forest University, Winston-Salem, North Carolina.
J Toxicol Environ Health. 1994 Oct;43(2):197-211. doi: 10.1080/15287399409531915.
In an accompanying article (see pp. 183-196), it was reported that administration of very high doses of the chlorotriazine herbicides atrazine, simazine, and diaminochlorotriazine (DACT), a common metabolite, expressed antiestrogenic activity in uteri of female Sprague-Dawley rats without expressing intrinsic estrogenic activity. In the present article, studies of chlorotriazine interaction with rat uterine estrogen receptors (ER) are reported. Under equilibrium conditions, none of the triazine compounds showed an ability to compete against binding of radiolabeled estradiol to ER. A weak competition was evident only if cytosols were preincubated with triazines at 25 degrees C prior to introduction of tracer. Competition was very weak, with kl estimates of 10-100 microM. A limited Scatchard analysis suggested a competitive type of inhibition. Sucrose gradient analysis of cytosol incubations showed that triazine interaction with the 4S isoform of ER may be greater than with the 8S form. When administered to ovariectomized rats for 2 d at 300 mg/kg/d, atrazine, simazine, or DACT all reduced uterine ER binding capacity by approximately 30%. Results from the receptor binding studies indicated that triazine competition against ER binding occurred to a much lesser degree than inhibition of estrogen-mediated responses reported in accompanying articles. This suggests that the complete responses to triazines may include inhibition of events other than or in addition to ER binding of estrogen.
在一篇随附文章（见第183 - 196页）中，据报道，给予雌性Sprague-Dawley大鼠非常高剂量的氯三嗪除草剂阿特拉津、西玛津和一种常见代谢物二氨基氯三嗪（DACT）时，它们在大鼠子宫中表现出抗雌激素活性，而无内在雌激素活性。在本文中，报道了氯三嗪与大鼠子宫雌激素受体（ER）相互作用的研究。在平衡条件下，没有一种三嗪化合物显示出与放射性标记雌二醇竞争结合ER的能力。只有当在引入示踪剂之前将胞质溶胶与三嗪在25℃预孵育时，才明显存在微弱竞争。竞争非常微弱，解离常数估计值为10 - 100微摩尔。有限的Scatchard分析表明是竞争性抑制类型。对胞质溶胶孵育物的蔗糖梯度分析显示，三嗪与4S亚型ER的相互作用可能大于与8S形式的相互作用。当以300毫克/千克/天的剂量给去卵巢大鼠给药2天时，阿特拉津、西玛津或DACT均使子宫ER结合能力降低约30%。受体结合研究结果表明，三嗪与ER结合的竞争程度远低于随附文章中报道的对雌激素介导反应的抑制程度。这表明对三嗪的完整反应可能包括抑制雌激素与ER结合之外或之外的其他事件。
