Small Molecule Protection of Bone Marrow Hematopoietic Stem Cells
Technical Report,30 Sep 2014,29 Sep 2017
University of Washington Seattle United States
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During the above project period we 1. demonstrated the ability of two small molecules, metformin and aminoguanidine, to improve growth, suppress aldehyde-induced DNA damage, and improve aldehyde dose-dependent survival of FANCG-deficient human cells. 2. used of a combination of chemical determination and dose-response assays to provide mechanistic insight into likely mechanisms by which each small molecule provides aldehyde dose-dependent protection in human cells. 3. developed a new quantitative formaldehyde-DNA adductcrosslink HPLC-MSMS assay. 4. small molecule suppression of markers of DNA damage in human cells in culture, and improved hematopoiesis and delayed cancer formation in a metformin-treated murine model of Fanconi anemia. 5. completed and published two manuscripts related to this work.
- Medicine and Medical Research
- Anatomy and Physiology