INTRACELLULAR XAS ON CULTURED MAMMALIAN CELLS TREATED WITH CR CARCINOGENS & DIET

用 CR 致癌剂处理的培养哺乳动物细胞的细胞内 XAS

• 批准号: 7598011
• 负责人: PETER A LAY
• 金额: $ 0.02万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-03-01 至 2008-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7598011
• 关键词: Adverse effects; Animals; Carcinogen Metabolism; Carcinogens; Cell Line; Cells; Chemistry; Complex; Computer Retrieval of Information on Scientific Projects Database; Cultured Cells; Diet; Electron Transport Complex III; Environment; Environmental Carcinogens; Funding; Grant; Human; Image; Institution; Ligands; Lung; Malignant Neoplasms; Malignant neoplasm of lung; Mammalian Cell; Measurement; Metabolic Biotransformation; Metalloproteins; Metals; Modeling; Muscle Cells; Mutagens; Occupational; Permeability; Pharmaceutical Preparations; Research; Research Personnel; Resources; Sampling; Source; Structure; Techniques; Tissues; United States National Institutes of Health; chromium hexavalent ion; dietary supplements; interest; metabolic abnormality assessment; programs

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The measurement of intracellular XANES and XAFS of bulk samples of cultured cells or of tissues can be used as a complementary technique to micro-XANES to determine the structures of metalloproteins, drugs, and metal carcinogens in an intracellular environment. Studies on Cr(VI) are of considerable interest as it is a widespread occupational and environmental carcinogen and, similarly, Cr(III) complexes are of interest because they have widespread applications as human and animal dietary supplements. In the current program, the cellular permeability and intracellular biotransformations of Cr carcinogens, mutagens, and dietary supplements will be studied in relation to Cr-induced cancers and the efficacy and side-effects of Cr dietary supplements. Specifically, the metabolism of carcinogens and mutagens will be studied in mammalian lung cells (the target for Cr-induced lung cancers). The intracellular chemistry of the dietary supplements will be studied with the same lung cell lines (to assess potential carcinogenic side-effects) and with human muscle cells to study the metabolism of these supplements and the effects on target cells. XANES imaging will also be examined for the differentiated muscle cells, which can be larger than 100 ¿m long. The XANES and XAFS will be compared with those of model complexes of Cr with biologically relevant ligands. Where there is evidence that the XANES is dominated by only one or two complexes, XAFS will also be used in order to investigate structural information in more detail.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以出现在其他 CRISP 条目中 列出的机构是。 对于中心来说，它不一定是研究者的机构。 对培养细胞或组织的大量样品进行细胞内 XANES 和 XAFS 测量可作为微 XANES 的补充技术，以确定细胞内环境中金属蛋白、药物和金属致癌物的结构。由于它是一种广泛的职业和环境致癌物，因此引起了人们极大的兴趣，同样，Cr(III) 复合物也引起了人们的兴趣，因为它们作为人类和动物膳食补充剂具有广泛的应用。将研究 Cr 致癌物、诱变剂和膳食补充剂的渗透性和细胞内生物转化与 Cr 诱发的癌症以及 Cr 膳食补充剂的功效和副作用。具体而言，将研究哺乳动物肺细胞中致癌物和诱变剂的代谢。 （铬诱发肺癌的目标）将使用相同的肺细胞系研究膳食补充剂的细胞内化学（以评估潜在的致癌副作用）和与人体肌肉细胞一起研究这些补充剂的新陈代谢，并且还将检查 XANES 成像对分化肌肉细胞的影响，这些细胞可能大于 100 ¿ m 长的 XANES 和 XAFS 将与 Cr 与生物学相关配体的模型复合物进行比较，如果有证据表明 XANES 仅由一种或两种复合物控制，XAFS 也将用于研究结构信息。更多细节。