EMBRYOTOXICITY OF ENVIRONMENTAL CHEMICALS

拟议研究的长期目标是更好地理解 外来有机化学品产生畸形和 胚胎发育中的其他形式的毒性。因为最近的研究如 表明胚胎酶系统可以催化 环境化学品中活性中间体的数量充足 为了引起容易观察到的严重畸形，这是 概述的研究是对特定胚胎生物激活的研究 酶系统。初步研究表明，至少有两个胚胎 P-45‘S(P-450c和P-450p)具有极显著的生物活性 活动。这项建议的目的是将重点放在这两个方面 血红素蛋白在胚胎中的生物激活潜能 纸巾。为了避免潜在的混淆的影响 母体因素，整个胚胎培养系统被选为 学习。这两种血球蛋白的分析将结合 底物探针分析、抑制物探针分析和免疫定量。 这些胚胎血色素蛋白调控模型的研究 将会被启动。这些方法的可行性已经得到了证明。 在初步实验中。啮齿动物胚胎与产前胚胎的比较 来自人类和亚人类灵长类动物的组织也将被制造出来。结果 从研究中获得的应该为卫生专业人员提供更多的 为孕妇提供关于以下方面的建议的合理依据 接触外国有机化学品。

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.