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

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，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测量可以作为微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。对铬（VI）的研究具有相当大的兴趣，因为它是一种广泛存在的职业和环境致癌物，同样，铬（III）配合物也具有广泛的应用，因为它们作为人类和动物的膳食补充剂。在目前的项目中，将研究Cr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Cr诱导的癌症以及Cr膳食补充剂的功效和副作用的关系。具体来说，将在哺乳动物肺细胞（cr诱导肺癌的靶点）中研究致癌物和诱变剂的代谢。我们将用相同的肺细胞系（以评估潜在的致癌副作用）和人体肌肉细胞来研究膳食补充剂的细胞内化学反应，以研究这些补充剂的代谢及其对靶细胞的影响。XANES成像还将检查分化的肌肉细胞，其长度可大于100米。XANES和XAFS将与具有生物相关配体的Cr模型配合物进行比较。如果有证据表明XANES仅由一个或两个复合物主导，XAFS也将用于更详细地调查结构信息。

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.