Biomarkers of Exposure to Hazardous Substances

接触有害物质的生物标志物

• 批准号: 7496664
• 负责人: BRUCE D HAMMOCK
• 金额: $ 2.5万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-04-01 至 2010-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7496664
• 关键词: Acute; Address; Air; Animals; Antibodies; Antioxidants; Apoptosis; Aromatic Hydrocarbons; Attention; Binding; Bioinformatics; Biological; Biological Assay; Biological Markers; Bioremediations; Breathing; Bronchoalveolar Lavage; Carbon; Cells; Chemicals; Chronic; Complex Mixtures; Data; Deposition; Development; Disulfides; Dose; Down-Regulation; Dyes; Eating; End Point; Environment; Enzymes; Epithelial; Epithelial Cells; Epithelium; Evaluation; Exclusion; Exposure to; Extracellular Protein; Fluorescence; Gene Expression; Gene Expression Profile; Goals; Hazardous Substances; Hazardous Waste Sites; Heat shock proteins; Heavy Metals; Histopathology; Human; Hydrocarbons; In Vitro; Invasive; Irrigation; Kidney; Label; Lateral; Liquid substance; Localized; Lung; Maintenance; Measures; Metabolic Activation; Metals; Methodology; Methods; Modeling; Molecular Chaperones; Molecular Profiling; Monitor; Movement; Naphthalene; Naphthalenes; Nasal Epithelium; Nasal Lavage Fluid; No-Observed-Adverse-Effect Level; Nose; Oxidation-Reduction; Pattern; Population; Predisposition; Process; Protein Disulfide Isomerase; Proteins; Proteome; Proteomics; RNA Interference; Rate; Rattus; Reaction; Reagent; Renal Tissue; Research; Research Support; Resolution; Respiratory System; Risk; Rodent; Role; Sampling; Screening procedure; Sentinel; Sister; Site; Small Interfering RNA; Soot; Structure of mucous membrane of nose; Sulfhydryl Compounds; Surface; System; Technology; Testing; Time; Tissues; Toxic effect; Toxicology; Training; Translations; Two-Dimensional Gel Electrophoresis; Urine; Water; Work; abstracting; accelerator mass spectrometry; adduct; base; biological adaptation to stress; body system; chemical release; cytotoxic; ethidium homodimer; ground water; hazard; improved; in vivo; innovation; interest; kidney cell; metabolomics; nephrotoxicity; new technology; nonhuman primate; novel; parental monitoring; particle; particle exposure; peroxiredoxin; programs; protein folding; remediation; renal epithelium; reproductive; research study; response; superfund site; toxicant; transcriptomics; urinary; vapor; wasting

DESCRIPTION (provided by applicant) Although our ability to analyze hazardous material in waste sites has improved dramatically in recent years, we are very limited in our ability to trace the movement of hazardous materials from Superfund sites through various media or to prioritize and mitigate the hazards involved. Our ability to predict exposure or effect of these materials on humans and their environment is still more limited. This Program consists of 8 integrated projects, 3 research support cores, a training core, a research translation core and an administrative core to address these problems. The investigators will determine the fate and transport of hazardous materials in ground water, surface water, and air as they move from toxic waste sites using classical and innovative methodologies. They will examine the effect of some of these materials using an epidemiological approach. Concurrently, they will develop sensitive systems for evaluating the exposure and effect of populations to these materials. Immunochemical, cell based and other systems will be used to detect biomarkers. Development of these biomarkers will be based on a fundamental understanding of the toxicological processes involved. The project will emphasize multiple organ systems with an in vivo emphasis on pulmonary and reproductive effects. New technologies for thermal and bioremediation of toxic waste will also be explored, and possible health risks associated with these technologies will be addressed. Rapid immunochemical and cell based analysis will supplement classical technologies for the evaluation of sites, validating models of transport from these sites, as well as determining human susceptibility, exposure and effect. Modern mass spectral technology will be evaluated for monitoring parent hazardous chemicals as well as biomarkers of exposure and effect. The investigators are expanding the use of transcriptomics, proteomics, metabolomics and integrated bioinformatic technologies to discover new mechanisms of action of hazardous materials and biomarkers for their action. The biomarkers developed in this project will serve as biological dosimeters in epidemiological and ecological studies in this and sister projects. The technologies developed in the project will be tested at field sites and transferred to end users through a research translation core.

描述(由申请人提供) 尽管近年来我们分析废弃场中危险物质的能力有了很大提高，但我们通过各种媒体追踪来自超级基金地点的危险物质移动的能力非常有限，或者优先处理和减轻所涉及的危险。我们预测这些材料对人类及其环境的暴露或影响的能力仍然更加有限。该方案包括8个综合项目、3个研究支助核心、1个培训核心、1个研究翻译核心和1个行政核心，以解决这些问题。调查人员将使用经典和创新的方法确定有害物质在地下水、地表水和空气中的命运和运输，当它们从有毒废物地点转移时。他们将使用流行病学方法检查其中一些材料的效果。同时，他们将开发敏感的系统，以评估人口对这些材料的暴露和影响。免疫化学、细胞和其他系统将被用于检测生物标记物。这些生物标记物的开发将基于对所涉及的毒理学过程的基本了解。该项目将强调体内多器官系统，强调对肺部和生殖的影响。还将探索有毒废物的热修复和生物修复新技术，并解决与这些技术相关的可能的健康风险。快速免疫化学和基于细胞的分析将补充用于评估地点的经典技术，验证来自这些地点的运输模式，以及确定人类易感性、暴露和影响。将对现代质谱学技术进行评估，以监测母体危险化学品以及暴露和影响的生物标志物。研究人员正在扩大转录组、蛋白质组学、代谢组学和集成生物信息学技术的使用，以发现危险物质的新作用机制和其作用的生物标记物。在该项目中开发的生物标志物将在该项目和姊妹项目的流行病学和生态学研究中作为生物剂量计。该项目开发的技术将在实地进行测试，并通过研究翻译核心转让给最终用户。