Investigation of antiestrogenic properties of unleaded gasoline in female mice.
Investigation of antiestrogenic properties of unleaded gasoline in female mice.
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无铅汽油对雌性小鼠的抗雌激素特性的研究。
DOI：
10.1006/taap.1994.1157
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发表时间：
1994
影响因子：
3.8
通讯作者：
Goldsworthy,TL
中科院分区：
文献类型：
--
作者：
Standeven,AM;Blazer3rd,DG;Goldsworthy,TL
雌性 B6C3F1 小鼠长期暴露于高浓度无铅汽油 (UG) 蒸气会诱发肝脏肿瘤，并引起子宫变化，提示雌激素拮抗作用。 UG 的这些作用可能是相关的，因为雌激素抑制小鼠肝癌的发生。本研究的目的是确定 UG 的抗雌激素特性是否可以在敏感的短期测定中得到证实。在体外测定从卵巢切除 (OVEX) 小鼠制备的子宫胞质中与雌激素受体的竞争性结合。 UG不抑制17-[3H]雌二醇(E2)与子宫胞质的特异性结合。为了确定UG是否诱导雌激素代谢，从用玉米油（对照）或UG（1800毫克/千克/天）胃插管（ig）处理3天的雌性小鼠制备肝细胞悬液。在体外定量测定中，从 UG 处理的小鼠中分离出的肝细胞将 E2 和 17-乙炔雌二醇转化为水溶性代谢物，其速度比对照肝细胞快三倍。剂量反应研究证实，低至 600 mg/kg/天的 UG 剂量即可诱导 E2 代谢。在为期 3 天的子宫营养测定中，用 UG（600 或 1800 mg/kg/天，ig）和 E2（1 µg/天，sc）联合治疗的未成熟雌性小鼠与用玉米油和 E2 联合治疗的小鼠具有相似的相对子宫重量和子宫过氧化物酶活性。在改进的子宫营养测定中，在第 1-4 天用玉米油或 UG（2400 mg/kg/天，ig）处理并在第 3-4 天用 E2（4μg/kg/天，sc）共同处理的 OVEX 小鼠在第 5 天具有相似的子宫重量。因此，虽然用 UG ig 处理小鼠在分离的肝细胞中诱导雌激素代谢，但根据通过测量测量，这种诱导并没有产生功能性抗雌激素后果。子宫营养测定。 These data suggest that the uterine effects caused by chronic exposure of mice to UG vapor may not be due to direct antiestrogenic effects of UG.
Chronic exposure of female B6C3F1 mice to a high concentration of unleaded gasoline (UG) vapor induced liver tumors and caused uterine changes suggestive of estrogen antagonism. These effects of UG may be related, since estrogens inhibit hepatocarcinogenesis in mice. The purpose of this study was to determine if antiestrogenic properties of UG could be demonstrated in sensitive short-term assays. Competitive binding to estrogen receptors was assayed in vitro in uterine cytosols prepared from ovariectomized (OVEX) mice. UG did not inhibit specific binding of 17 -[3H]estradiol (E2) to uterine cytosols. To determine if UG induced estrogen metabolism, hepatocyte suspensions were prepared from female mice treated by intragastric intubation (ig) for 3 days with corn oil (control) or UG (1800 mg/kg/day). In a quantitative in vitro assay, hepatocytes isolated from UG-treated mice converted E2 and 17 -ethinyl estradiol to water soluble metabolites at a three-fold faster rate than control hepatocytes. Dose-response studies confirmed the induction of E2 metabolism by UG doses as low as 600 mg/kg/ day. In a 3-day uterotrophic assay, immature female mice cotreated with UG (600 or 1800 mg/kg/day, ig) and E2 (1 ?g/day, sc) had similar relative uterus weights and uterine peroxidase activity as mice cotreated with corn oil and E2. In a modified uterotrophic assay, OVEX mice treated with corn oil or UG (2400 mg/kg/day, ig) on Days 1-4 and cotreated with E2 (4 ?g/kg/day, sc) on Days 3-4 had similar uterus weights on Day 5. Thus, while ig treatment of mice with UG induced estrogen metabolism in isolated hepatocytes, this induction did not have functional antiestrogenic consequences as measured by uterotrophic assays. These data suggest that the uterine effects caused by chronic exposure of mice to UG vapor may not be due to direct antiestrogenic effects of UG.