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AGENTS TO INDUCE IMMUNOTOXICITY

诱导免疫毒性的药物

基本信息

批准号：
6325516
负责人：
KIMBER WHITE
金额：
$ 42.17万
依托单位：
VIRGINIA COMMONWEALTH UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2000
资助国家：
美国
起止时间：
2000-07-01 至 2005-06-30
项目状态：
已结题

项目摘要

This contact was established to evaluate the potential for environmental agents, therapeutic drugs or biological materials to induce immunotoxicity, altered hypersensitivity responses or autoimmune disease in rodent models. This is accomplished via three mechanisms. The first mechanism is to examine the ability of test chemical to modulate immune responses using a defined and validated panel of immune function tests, host resistance models and hypersensitivity assays in rodents. These studies will provide assessment of the potential hazards of human exposure and increase the database regarding the number of chemicals which affect the immune system. A second objective is to develop and validate new methodologies and make use of advancements in the fields of molecular biology and toxicology, to increase the predictive value of the standardized testing panels used to evaluate immunotoxicity. Examples of such new developments include the use of the RNAse protection assay to establish cytokine profiles for chemical irritants and sensitizers. Finally, studies conducted under this contract will address the underlying cellular and molecular basis for observed alterations in immune functions. Molecular techniques such as RT-PCR, analysis of cell activation markers and evaluation of targeted cell subpopulations will help elucidate the specific cellular targets of immunotoxic agents and suggest potential strategies for minimizing risks to the human population.

建立这种联系是为了评估环境因素、治疗药物或生物材料在啮齿动物模型中诱导免疫毒性、改变的超敏反应或自身免疫性疾病的可能性。这是通过三种机制实现的。第一种机制是使用一组确定和验证的免疫功能测试、宿主抗性模型和啮齿动物的超敏反应测试来检查测试化学物质调节免疫反应的能力。这些研究将提供对人类暴露的潜在危险的评估，并增加关于影响免疫系统的化学物质数量的数据库。第二个目标是开发和验证新的方法，并利用分子生物学和毒理学领域的进展，增加用于评估免疫毒性的标准化测试小组的预测价值。这类新发展的例子包括使用核糖核酸酶保护试验来建立化学刺激物和增敏剂的细胞因子图谱。最后，根据该合同进行的研究将解决观察到的免疫功能变化的潜在细胞和分子基础。诸如RT-PCR、细胞激活标记分析和目标细胞亚群评估等分子技术将有助于阐明免疫毒剂的特定细胞靶点，并提出将对人类群体的风险降至最低的潜在策略。