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

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。大量培养细胞或组织样品的XANES和XAFS测量可作为微量XANES的补充技术，用于确定细胞内环境中金属蛋白、药物和金属致癌物的结构。铬(VI)是一种广泛的职业致癌物和环境致癌物，对它的研究很有兴趣，同样，铬(III)络合物也是人们感兴趣的，因为它们在人类和动物的饮食补充剂中有着广泛的应用。在目前的计划中，将研究铬致癌物、诱变剂和膳食补充剂的细胞渗透性和细胞内生物转化与铬诱发癌症的关系，以及铬膳食补充剂的疗效和副作用。具体地说，致癌物和诱变剂的代谢将在哺乳动物肺细胞(铬诱发肺癌的靶点)中进行研究。这些膳食补充剂的细胞内化学成分将在相同的肺细胞系(以评估潜在的致癌副作用)和人类肌肉细胞中进行研究，以研究这些补充剂的新陈代谢和对靶细胞的影响。XANES成像还将检查分化的肌肉细胞，其长度可以超过100？m。XANES和XAFS将与铬与生物相关配体的模型络合物进行比较。如果有证据表明XANES只由一个或两个复合体主导，XAFS也将被用来更详细地研究结构信息。

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.