MECHANISTIC STUDIES OF OVARIAN TOXICITY

卵巢毒性的机制研究

• 批准号: 2574291
• 负责人: B DAVIS
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/2574291
• 关键词: aromatic hydrocarbon receptor; brca gene; cell cycle; chemical carcinogenesis; cytotoxicity; environmental toxicology; ethers; hormone biosynthesis; hormone regulation /control mechanism; human tissue; in situ hybridization; laboratory mouse; laboratory rat; ovary; ovary neoplasms; prostaglandin endoperoxide synthase; tissue /cell culture

In 1996 we continued to examined the effects of ethylene glycol monmeethyl ether (EGME) on ovarian function. To better predict potential human health risks, we examined the effects of the proximate metabolite of EGME, 2-methoxy acetic acid or MAA, on primary cultures of human luteal cells. We found that the human luteal cell response to MAA is quite comparable to the rat luteal cell response in vitro, and predicit this data will be used to help determine acceptable exposure limits in women. We have also described the development of ovarian tumors in adult female Sprague-Dawley rats exposed to TCDD (dioxin) and are currently determining the tumor morphology and origin, and determining whether the ovary and these tumors have the Ah receptor. We also continued to examine the in situ expression of BRCA1 in the mouse ovary and have demonstrated that BRCA1 expression is independent of hormonal stimulation, but is dependent on the cell cycle. We are also developing probes for in situ hybridization studies of BRCA1 in the rat, and BRCA2 in the mouse and the rat. Finally, we are defining the role of cyclooxygenase 1 and cycloxygenase 2 (COX 1 and COX 2) in the ovary using the mice defecient in these enzymes and have established that COX2 is necessary for ovulation induction.

1996年，我们继续研究了乙二醇的影响， 单甲醚（EGME）对卵巢功能的影响。为了更好地预测 人类健康风险，我们研究了近代谢物的影响 EGME、2-甲氧基乙酸或MAA对人的原代培养物 黄体细胞 我们发现人黄体细胞对MAA的反应是 与大鼠黄体相当 细胞反应，并预测这些数据将用于帮助 确定女性可接受的接触限值。 我们还描述了 成年雌性Sprague-Dawley大鼠卵巢肿瘤的发生 暴露于TCDD（二恶英），目前正在确定肿瘤 形态和起源，并确定卵巢和这些肿瘤是否 有Ah受体。 我们还继续研究了 BRCA 1在小鼠卵巢中的表达，并已证明BRCA 1 表达不依赖于激素刺激，但依赖于 细胞周期 我们也在开发原位杂交的探针 在大鼠中的BRCA 1研究，以及在小鼠和大鼠中的BRCA 2研究。 最后，我们定义了环氧合酶1和环氧合酶 2（考克斯1和考克斯2）在卵巢中使用这些缺陷的小鼠。 酶，并已确定COX 2是排卵所必需的， 诱导