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

该子项目是利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得主要资金， 因此可以在其他CRISP条目中表示。列出的机构是 中心，不一定是研究者的机构。 细胞内XANES和培养细胞或组织的大量样品的XAFS的测量可用作微XANES的补充技术，以确定细胞内环境中的金属蛋白、药物和金属致癌物的结构。对Cr（VI）的研究是相当感兴趣的，因为它是一种广泛的职业和环境致癌物，同样，Cr（III）络合物是感兴趣的，因为它们作为人类和动物膳食补充剂具有广泛的应用。 在目前的计划中，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将研究与铬诱导的癌症和铬膳食补充剂的疗效和副作用。 具体而言，将在哺乳动物肺细胞（铬诱导肺癌的靶细胞）中研究致癌物和诱变剂的代谢。 将使用相同的肺细胞系（以评估潜在的致癌副作用）和人类肌肉细胞研究膳食补充剂的细胞内化学，以研究这些补充剂的代谢和对靶细胞的影响。XANES成像还将检查分化的肌肉细胞，这些细胞可以大于100微米长。 的XANES和XAFS将进行比较与那些模型络合物的铬与生物相关的配体。 如果有证据表明XANES仅由一种或两种复合物主导，XAFS也将用于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.