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Iron is an
essential element for humans and most other organisms. It is crucial for
processes such as oxygen transport, energetic metabolism (oxidative
phosphorylation), detoxification of chemicals, synthesis of DNA and many
others. On the other hand, the excess of free iron can participate in oxidative
stress reactions with the production of free radicals (Fenton’s chemistry) and
may cause severe tissue damage. That is why both systemic and intracellular
iron levels must be tightly regulated. Iron, not surprisingly, plays an
important role in many pathological conditions like neurodegenerative diseases
and cancer.
The
project was focused on cancer study and was divided in two parts- chemical and
biological. First step was concentrate on characterization of complexation
possibilities newly synthesised chelators. The titrations with ferric and
ferrous ions were performed. The chelators with highest affinity to irons ions
were chosen for advanced studies. The project covers in vitro cytotoxic studies
on different types of tumor cell lines (MiaPaca, Patu, Capan), MTT assay was
used to establish IC 50. Cytotoxic effect of chelators on tumor cell lines was
compared with cytotoxicity on human fibroblasts (healthy cell lines). Imaging
possibilities of fluorescent chelators were studied as well. The fluorescent
chelators were able to cross cellular membranes, in concentration of 1uM and
thus provide us the image of their intracellular transport, subcellular
localization and intracellular redistribution. For in vivo imaging nu/nu
mice with suppressed immune system were used. The distribution of fluorescence
chelators after administration was visualized by Xtreme device (Brucker).
Keywords: Iron, Chelators, Imaging, Tumor diseases, Cytotoxicity
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