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Lead (Pb), cadmium (Cd) and uranium (U) present no known biological function but are toxic in various concentration ranges. Pb and Cd lead generally to nephrotoxicity consisting in proximal renal tubular dysfunction and accumulation while U has been reported to induce chemical kidney toxicity, functional and histological damages being as well mainly observed in proximal tubule cells. This work address the question of Cd, Pb, and U cytotoxicity, intracellular accumulation and repartition after acute intoxication of renal proximal tubule epithelial cells. After cells exposure to different concentrations of metals for various times, morphological changes were observed and intracellular concentrations and distributions of toxic metals were specified by PIXE coupled to RBS. Cell viability, measured by biochemical tests, was used as toxicity indicator. A direct correlation between cytotoxicity and intracellular accumulation in renal epithelial cells have been established. Finally, intracellular Pb and U localizations were detected while Cd was found to be uniformly distributed in renal cells.
Human nails were analyzed by PIXE measurements using focused 3MeV Si2+ and 2MeV proton beams. It was found that the 3MeV Si2+ ions have a higher sensitivity for sodium and aluminium, on the other hand, 2MeV protons have a higher sensitivity for sulfur, potassium and calcium in nails. By using 3MeV Si2+ microprobe, it was observed that the sodium is distributed uniformly with some depletion areas and that aluminium segregates in grains. It shows an advantage of a heavy ion microprobe over a proton microprobe.
The status of the field of analysis of biological material using PIXE and complementary ion beam techniques are discussed. The development of PIXE with relevance to biology and the future prospects of Bio-PIXE are described.
Nuclear microprobe analysis studies in cancer cell pharmacology and biology carried out at Bordeaux-Gradignan are reported. The cellular pharmacology of two anticancer agents, cis-diammine-dichloroplatinum(II), and 4′-iodo-4′-deoxy-doxorubicin, were investigated, as well as the role of iron in neuroblastoma carcinogenesis, and chromium(III) in trans-generation carcinogenesis. Nuclear microprobe analysis, using PIXE and particle backscattering microanalysis, was able to reveal intracellular and tissue distributions of the elements under investigation. Moreover, the fully quantitative and multi-elemental character of nuclear microprobe analysis offered information on possible mechanisms of drug action, metal carcinogenesis, and interactions with endogenous trace elements in cancer cells.