EMBRYOTOXICITY OF ENVIRONMENTAL CHEMICALS

环境化学品的胚胎毒性

• 批准号: 3251900
• 负责人: MONT R JUCHAU
• 金额: $ 23.13万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-04-01 至 1991-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3251900
• 关键词: Primates; acetylaminofluorene; biotransformation; congenital skeletal disorder; cyclophosphamide; cytochrome P450; diethylstilbestrol; early embryonic stage; embryo /fetus culture; environmental toxicology; enzyme induction /repression; enzyme linked immunosorbent assay; enzyme mechanism; estradiol; hemoprotein; human tissue; immunodiffusion; immunoelectrophoresis; laboratory rat; prenatal growth disorder; radioimmunoassay; rifamycins; teratogens; toxicant interaction

The long-range goal of the proposed research is to better understand mechanisms whereby foreign organic chemicals produce malformations and other forms of toxicity in developing embryos. Because recent research as indicated that embryonic enzyme systems can catalyze conversion of environmental chemicals to quantities of reactive intermediates sufficient to elicit readily observalbe gross malformations, an integral aspect of the outlined investigation is the study of specific embryonic bioactivating enzyme systems. Preliminary studies suggest that at least two embryonic P-45's (P-450c and P-450p) can effect highly significant bioactivating activity. It is the intention of this proposal to focus on these two hemoproteins in terms of their bioactivating potential in embryonic tissues. In order to avoid the influence of potentially confounding maternal factors, the whole embryo culture system has been chosen for study. The two hemoproteins will be analyzed with a combination of substrate probe analyses, inhibitor probe analyses and immunoquantitation. Investigations of the models of regulation of these embryonic hemoproteins will be initiated. The feasibiity of the approaches has been demonstrated in preliminary experiments. Comparisons of rodent embryos with prenatal tissues from humans and subhuman primates will also be made. Results obtained from the research should provide health professionals a more rational basis for providing advice to pregnant women with respect to their exposure to foreign organic chemicals.

拟议研究的远程目标是更好地了解 外国有机化学物质产生畸形的机制和 在发展胚胎中的其他形式的毒性。 因为最近的研究是 表明胚胎酶系统可以催化 环境化学物质到足够的反应性中间体 为了引起很容易观察畸形的畸形，这是不可或缺的方面 概述的研究是对特定胚胎生物活化的研究 酶系统。 初步研究表明至少两个胚胎 P-45的（P-450C和P-450p）可以影响高度显着的生物活化 活动。 该提议的目的是专注于这两个 血蛋白在胚胎中的生物活化潜力方面 组织。 为了避免潜在混淆的影响 孕产妇因素，已选择整个胚胎培养系统 学习。 两种血蛋白将通过结合 底物探针分析，抑制剂探针分析和免疫常规。 研究这些胚胎血蛋白的调节模型 将开始。 已经证明了这些方法的流行性 在初步实验中。 啮齿动物胚胎与产前的比较 还将制造来自人类和亚人类灵长类动物的组织。 结果 从研究中获得的应该为卫生专业人员提供更多 为孕妇提供建议的理性基础 暴露于外国有机化学物质。