SHORT-TERM EFFECTS OF CHLOROTRIAZINES ON ESTRUS IN FEMALE SPRAGUE-DAWLEY AND FISCHER-344 RATS
SHORT-TERM EFFECTS OF CHLOROTRIAZINES ON ESTRUS IN FEMALE SPRAGUE-DAWLEY AND FISCHER-344 RATS
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DOI：
10.1080/15287399409531912
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发表时间：
1994-10-01
期刊：
影响因子：
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通讯作者：
STEVENS, JT
中科院分区：
文献类型：
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作者：
ELDRIDGE, JC;FLEENORHEYSER, DG;STEVENS, JT
雌性Sprague-Dawley和Fischer 344大鼠连续2周每天经口给予100或300 mg/kg的阿特拉津或西玛津（s-氯三嗪），以评价对体重、卵巢、子宫和肾上腺重量、发情周期阶段、阴道细胞学和血浆激素（雌二醇、孕酮、催乳素和皮质酮）水平的影响。在两个剂量水平下，Sprague-Dawley和Fischer 344雌性大鼠的体重均显著降低，同时卵巢和子宫重量显著降低，循环雌二醇水平降低。Fischer 344大鼠的影响程度低于Sprague-Dawley大鼠，西玛津的影响不如相同剂量的阿特拉津明显。两种染料的最大耐受剂量（MTD：大于或等于体重减轻10%）估计为阿特拉津100 mg/kg，西玛津300 mg/kg。Sprague-Dawley雌性大鼠表现出处理相关的发情周期延长和皮质上皮细胞特征天数增加。这导致发情周期天数百分比增加，间情周期天数百分比减少。阿特拉津给药的Fischer 344雌性动物也表现出明显的周期延长趋势，但这是由于发情期周期百分比减少和死亡天数增加所致。这些结果表明，在Sprague-Dawley大鼠中，以等于或高于MTD的三嗪剂量进行治疗可能会导致内源性雌激素的长期暴露，但Fischer 344大鼠不会。这些变化可能解释了在氯三嗪处理的雌性Sprague-Dawley大鼠中观察到的早期发病和/或乳腺肿瘤发病率增加。已知该品系大鼠随着年龄的增长容易发生乳腺肿瘤的实质性发展，而Fischer 344品系不太可能表现出这种反应。
Atrazine or simazine (s-chlorotriazines) was administered by gavage daily for 2 wk to female Sprague-Dawley and Fischer 344 rats at oral doses of 100 or 300 mg/kg to evaluate effects on body, ovary, uterus, and adrenal weights, estrous cycle stages, vaginal cytology, and plasma hormone (estradiol, progesterone, prolactin, and corticosterone) levels. Significant reductions in body weights of both Sprague-Dawley and Fischer 344 female rats at both dose levels were accompanied by a significant reduction in ovarian and uterine weights, and a decrease in circulating estradiol levels. The magnitudes of the effects were less in Fischer 344 rats than in Sprague-Dawley rats, and the effects of simazine were less pronounced than those of atrazine at the same dose. A maximum tolerated dose (MTD: greater than or equal to 10% body weight reduction) was estimated to be 100 mg/kg for atrazine and 300 mg/kg for simazine for both stains. The Sprague-Dawley female rats exhibited a treatment-related lengthening of the estrous cycle and an increased number of days characterized by cornified epithelial cells. This resulted in a greater percent of the cycle days spent in estrus and reduction in the percent of the cycle days spent in diestrus. Atrazine-dosed Fischer 344 females also exhibited a significant trend toward cycle lengthening, but this was due to reduction in the percent of cycle spent in estrus and a concomitant increase in diestrual days. These findings suggest that treatment with doses of triazine at or above the MTD may result in prolonged exposure to endogenous estrogen in the Sprague-Dawley but not the Fischer 344 rat. These changes may account for the observed earlier onset and/or increased incidence of mammary tumors in chlorotriazine-treated female Sprague-Dawley rats. This strain of rat is already known to be prone to a substantial development of mammary tumors with advancing age, while the Fischer 344 strain is not as likely to exhibit this response.