Estrous cycle patterns of Sprague-Dawley rats during acute and chronic atrazine administration
Estrous cycle patterns of Sprague-Dawley rats during acute and chronic atrazine administration
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DOI：
10.1016/s0890-6238(99)00056-8
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发表时间：
1999-11-01
影响因子：
3.3
通讯作者：
Tyrey, L
中科院分区：
文献类型：
--
作者：
Eldridge, JC;Wetzel, LT;Tyrey, L
乳腺肿瘤 (MT) 发病率增加或较早发病与终生喂养斯普拉格-道利 (SD) 雌性大鼠阿特拉津（一种农业除草剂）有关。由于 MT 在该品系中自发发生，并伴有持续发情和无环雌激素分泌，因此有人提出莠去津可能会促进这一过程。对 7 至 8 周龄的 SD 雌性大鼠施用莠去津，同时监测阴道细胞学。灌胃给药 200 mg/kg/d 时，明显超过了最大耐受剂量 (MTD)，主要的早期反应是延长阴道发情间期。持续发情期也有出现，但较少见。当在饮食中添加莠去津时，同样在 400 ppm 浓度下最初出现延长发情间期，但在测试 13 至 14 周（20 至 21 周龄）时，持续发情占主导地位，在测试 26 周时，动物的发情间期上升至 > 50%。年龄匹配的对照组也表现出持续发情，但程度较轻。在 400 ppm 阿特拉津持续 6 个月的情况下，动物在所有天数中平均有 62.8% 表现出阴道发情，而年龄匹配的对照组为 47.3%，幼龄动物为 20% 至 25%。 400 ppm 的剂量也超过了 MTD。观察到的对动情周期和体重变化无影响的水平为 50 ppm。对发情周期的显着影响仅发生在先前与增强或过早 MT 形成相关的水平上，这表明衰老 SD 雌性大鼠的肿瘤反应可以通过控制内部雌激素环境的因素来操纵。由于莠去津没有内在的雌激素活性，因此对易感动物模型进行高剂量给药更有可能改变对排卵和正常周期的控制。过量剂量水平的要求以及神经内分泌衰老的差异使得这种作用方式对人类健康的风险基本上不存在。 (C) 1999 Elsevier Science Inc. 保留所有权利。
An increased incidence or earlier onset of mammary tumors (MT) has been associated with lifetime feeding of atrazine, an agricultural herbicide, to Sprague-Dawley (SD) female rats. Because MT occur spontaneously in this strain, along with episodes of persistent estrus and acyclic estrogen secretion, it was proposed that atrazine may act to promote this process. SD female rats, 7 to 8 wks old, were administered atrazine while vaginal cytology was monitored. At 200 mg/kg/d by gavage, which clearly exceeded the maximum tolerated dose (MTD), the predominant early response was prolonged vaginal diestrus. Persistent estrous episodes were seen, but less commonly. When atrazine was added to the diet, there was likewise an initial appearance of prolonged diestrus at 400 ppm, but by 13 to 14 wks on test (20 to 21 wks of age), persistent estrus was predominant, rising to >50% of animals by 26 wks on test. Age-matched controls also displayed persistent estrus, but to a lesser degree. At 400 ppm atrazine for 6 mo, animals displayed vaginal estrus for a mean of 62.8% of all days, versus 47.3% in age-matched controls, and 20 to 25% in young animals. The 400 ppm dose also exceeded the MTD. Observed no-effect levels for estrous cycling and body weight change were 50 ppm. Significant effects on estrous cycling occurred only at levels previously associated with enhanced or premature MT formation, and suggest that the tumor response in aging SD female rats can be manipulated by factors controlling the internal estrogen milieu. Because atrazine has no intrinsic estrogenic activity, it is more likely that high-level dosing to a susceptible animal model alters control of ovulation and normal cycling. The requirement of excessive dosing levels, as well as differences in neuroendocrine senescence, makes a risk to human health from this mode of action essentially nonexistent. (C) 1999 Elsevier Science Inc. All rights reserved.