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Electron paramagnetic resonance study of peripheral blood mononuclear cells from patients with refractory solid tumors treated with Triapine.

Abstract
The metal chelator Triapine, 3-aminopyridine-2-carboxaldehyde thiosemicarbazone, is a potent inhibitor of ribonucleotide reductase. EPR spectra consistent with signals from Fe-transferrin, heme, and low-spin iron or cupric ion were observed in peripheral blood mononuclear cells (PBMCs) obtained from patients treated with Triapine. One signal that is unequivocally identified is the signal for Fe-transferrin. It is hypothesized that Fe uptake is blocked by reactive oxygen species generated by FeT(2) or CuT that damage transferrin or transferrin receptor. A potential source for the increase in the heme signal is cytochrome c released from the mitochondria. These results provide valuable insight into the in vivo mechanism of action of Triapine.
AuthorsJill M Kolesar, William R Schelman, Peter G Geiger, Kyle D Holen, Anne M Traynor, Dona B Alberti, James P Thomas, Christopher R Chitambar, George Wilding, William E Antholine
JournalJournal of inorganic biochemistry (J Inorg Biochem) Vol. 102 Issue 4 Pg. 693-8 (Apr 2008) ISSN: 0162-0134 [Print] United States
PMID18061679 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
Chemical References
  • Pyridines
  • Thiosemicarbazones
  • 3-aminopyridine-2-carboxaldehyde thiosemicarbazone
  • Cytochromes c
Topics
  • Cytochromes c (metabolism)
  • Electron Spin Resonance Spectroscopy
  • Humans
  • Monocytes (chemistry)
  • Neoplasms (drug therapy)
  • Pyridines (therapeutic use)
  • Thiosemicarbazones (therapeutic use)

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