BIOLOGICAL INDICATORS OF TOXICITY FROM SEMICONDUCTORS

半导体毒性的生物指标

• 批准号: 3253171
• 负责人: BRUCE A FOWLER
• 金额: $ 20.62万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-05-16 至 1993-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3253171
• 关键词: aminohydrolases; arsenic; atomic absorption spectrometry; cells; cytotoxicity; decarboxylases; electron microscopy; enzyme mechanism; erythrocytes; gallium; gel filtration chromatography; hamsters; heme; high performance liquid chromatography; indium; injury; laboratory rat; ligase; liver cells; metal metabolism; metal poisoning; oxidoreductase; porphobilinogen synthase; porphyrin biosynthesis; renal tubule; semiconduction; statistics /biometry; tissue /cell culture; urinalysis

The proposed studies are focussed on further delineation between biologically active chemical species of Ga, In or As and early biological indicators of target cell injury. These studies will involve in vivo exposure of rats and hamsters to intratracheal instillations and intraperitoneal injections of Ga, In As, GaAs, or InAs. Target tissue concentrations of these elements will be fractioned into inorganic, macromolecular and organelle components using a variety of analytical and biochemical methodologies. These data will be correlated with metal or mixture-specific biochemical responses involving perturbations of heme biosynthetic pathway enzyme activities in order to delineate mechanisms, sensitivity and specificity of alterations in the pathway by these elements on an individual or mixture basis in blood, liver and kidney. These data will be quantitatively correlated with ultrastructural morphometric analyses of blood, liver cells and renal proximal tubule cells in situ and tissue heme biosynthetic pathway enzymes in order to delineate which of these indicator classes is the best indicator for cell injury form chemical species of Ga, In or As either alone or in mixture combinations. In order to further delineate mechanistic relationships between intracellular chemical species of these elements, the biological indicators and mechanisms of cell injury, in vitro studies using red blood cells and primary hepatocyte and renal tubule epithelial cell cultures will be conducted during the second phase of the project. These studies will be conducted using stable soluble chemical forms of Ga, In and As. Results of these studies should yield new insights into the necessary relationships between specific intracellular chemical species of Ga, In or As, early metal-specific biochemical responses to these agents and novel biological indicators of target cell injury following acute intratracheal instillation of particulates of these elements, either alone or in combination.

拟议的研究重点是进一步划分 Ga、In 或 As 的生物活性化学物质和早期生物 靶细胞损伤的指标。 这些研究将涉及体内 大鼠和仓鼠暴露于气管内滴注和 腹膜内注射 Ga、In As、GaAs 或 InAs。 靶组织 这些元素的浓度将被分解为无机物， 使用各种分析和方法分析大分子和细胞器成分 生化方法学。 这些数据将与金属或 涉及血红素扰动的混合物特异性生化反应 生物合成途径酶活性以描述机制， 这些元件改变途径的敏感性和特异性 以血液、肝脏和肾脏中的个体或混合物为基础。 这些数据将与超微结构定量相关 血液、肝细胞和肾近曲小管细胞的形态测定分析 原位和组织血红素生物合成途径酶，以描绘 这些指标类别中哪一个是细胞损伤形式的最佳指标 Ga、In或As的化学物质可以是单独的或者是混合物的组合。 为了进一步阐明二者之间的机械关系 这些元素的细胞内化学物质，生物指标 和细胞损伤的机制，使用红细胞和的体外研究 原代肝细胞和肾小管上皮细胞培养物 在项目的第二阶段进行。 这些研究将 使用稳定的可溶化学形式 Ga、In 和 As 进行。 结果 这些研究应该会对必要的关系产生新的见解 Ga、In 或 As 的特定细胞内化学物质之间，早期 对这些试剂和新型生物的金属特异性生化反应 急性气管内滴注后靶细胞损伤指标 这些元素的颗粒，单独或组合。