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

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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.