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):183-96. doi: 10.1080/15287399409531914.
Several published reports have indicated that certain chloro-s-triazine herbicides may alter endocrine function in rats, possibly by androgen receptor binding. In direct tests of estrogenic bioactivity, oral doses of up to 300 mg/kg/d of atrazine, simazine, or the common metabolite diaminochlorotriazine (DACT) did not significantly increase uterine weight of ovariectomized Sprague-Dawley female rats. The highest dose, which was approximately 10% of the LD50 for these compounds, did cause body weight loss. When administered concomitantly with sc injections of estradiol (2 micrograms/kg), 300 mg/kg of orally administered chlorotriazines significantly reduced uterine weight in comparison to animals given estrogen alone. Neither atrazine, simazine, nor DACT, at oral doses up to 300 mg/kg/d, stimulated incorporation of [3H]thymidine into uterine DNA of immature Sprague-Dawley female rats. However, oral treatment at doses of 50 mg/kg and higher significantly reduced thymidine incorporation into uterine DNA extracted from immature rats given a single injection of 0.15 microgram estradiol. Oral doses of 300 mg/kg of atrazine, simazine, or DACT significantly reduced expression of progesterone receptor binding in cytosol fractions prepared from uteri of ovariectomized rats injected sc with 1 microgram estradiol; 50 mg/kg triazine was not effective in this case. Uterine progesterone receptor levels were not stimulated in rats given oral doses up to 300 mg/kg of these triazines without estradiol injections. These results suggest that atrazine, simazine, and DACT possess no intrinsic estrogenic activity but that they are capable of weak inhibition of estrogen-stimulated responses in the rat uterus. This inhibition may play a role in the previously observed disruptive actions of chlorotriazines on reproductive endocrine function of female rats.
数篇已发表的报告指出，某些氯代-s-三嗪类除草剂可能会改变大鼠的内分泌功能，其作用机制可能是与雄激素受体结合。在雌激素生物活性的直接测试中，给去卵巢的斯普拉格-道利雌性大鼠口服高达300毫克/千克/天的莠去津、西玛津或常见代谢物二氨基氯三嗪（DACT），并未显著增加其子宫重量。最高剂量约为这些化合物半数致死量的10%，确实导致了体重减轻。当与皮下注射雌二醇（2微克/千克）同时给药时，与单独给予雌激素的动物相比，口服300毫克/千克的氯代三嗪显著降低了子宫重量。口服剂量高达300毫克/千克/天的莠去津、西玛津或DACT，均未刺激未成熟的斯普拉格-道利雌性大鼠子宫DNA中[3H]胸腺嘧啶核苷的掺入。然而，以50毫克/千克及更高剂量进行口服治疗，显著降低了从单次注射0.15微克雌二醇的未成熟大鼠中提取的子宫DNA中胸腺嘧啶核苷的掺入量。口服300毫克/千克的莠去津、西玛津或DACT，显著降低了从皮下注射1微克雌二醇的去卵巢大鼠子宫制备的胞质组分中孕酮受体结合的表达；在这种情况下，50毫克/千克的三嗪无效。在未注射雌二醇的情况下，给大鼠口服高达300毫克/千克的这些三嗪，并未刺激子宫孕酮受体水平。这些结果表明，莠去津、西玛津和DACT不具有内在雌激素活性，但它们能够微弱抑制雌激素对大鼠子宫的刺激反应。这种抑制作用可能在先前观察到的氯代三嗪对雌性大鼠生殖内分泌功能的破坏作用中发挥作用。
