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J Inorg Biochem. 2008 Apr;102(4):693-8. Epub 2007 Oct 30.

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

Author information

  • 1University of Wisconsin Paul P. Carbone Comprehensive Cancer Center, University of Wisconsin-Madison, 600 Highland Avenue, Room K4/554, Madison, WI 53792, USA. jmkolesar@pharmacy.wisc.edu

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.

PMID:
18061679
[PubMed - indexed for MEDLINE]
PMCID:
PMC2390869
Free PMC Article
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