EMBRYOTOXICITY OF ENVIRONMENTAL CHEMICALS

拟议研究的长期目标是更好地了解 外来有机化学物质产生畸形的机制， 其他形式的毒性在发育中的胚胎。 因为最近的研究 表明，胚胎酶系统可以催化转化 环境化学品到足够数量的活性中间体 容易引起严重的畸形，一个完整的方面， 概述的调查是研究特定的胚胎生物激活 酶系统 初步研究表明，至少有两个胚胎 P-450 c和P-450 p具有非常显著的生物活性 活动 本提案的目的是集中讨论这两个问题， 血红素蛋白在胚胎中生物活化潜力 组织中 为了避免潜在混杂因素的影响， 母体因素，选择了整个胚胎培养系统， study. 两种血红素蛋白将结合以下分析： 底物探针分析、抑制剂探针分析和免疫定量。 这些胚胎血红素蛋白调控模型的研究 将被启动。 这些方法的可行性已被证明 在初步实验中。 啮齿动物胚胎与产前胚胎的比较 还将制备来自人类和次人类灵长类动物的组织。 结果 从研究中获得的信息应该为卫生专业人员提供更多的 为孕妇提供咨询的合理依据， 暴露于外来有机化学物质

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.