Small Molecule Protection of Bone Marrow Hematopoietic Stem Cells

Abstract

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 adduct/crosslink HPLC-MS/MS 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.

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Document Details

Document Type
Technical Report
Publication Date
Dec 01, 2017
Accession Number
AD1047413

Entities

People

  • Raymond J. Monnat

Organizations

  • University of Washington

Tags

DTIC Thesaurus Topics

  • Blood
  • Cell Physiological Processes
  • Cells
  • Chemical Synthesis
  • Chemistry
  • Electrospray Ionization
  • Genetics
  • Health Services
  • Hematologic Diseases
  • Liquid Chromatography
  • Metabolic Diseases
  • Organic Chemistry
  • Stem Cells

Fields of Study

  • Medicine

Readers

  • Analytical Chemistry
  • Cellular and Molecular Pathways of Apoptosis.
  • Immunology and Pathology

Technology Areas

  • Biotechnology