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[Changes in the free-radical state and level of free iron during the formation of drug resistance in tumor cells].

Abstract
The development of resistance of K562 human erythroleukemia cells to doxorubicin, a widely used antitumor antibiotic with the prooxidant action, leads to changes in the free-radical state of cells. It has been found that the formation of superoxide anion in resistant cells decreases. The introduction of doxorubicin to the culture medium induced a considerably lesser increase in the formation of O2*- in resistant cells compared to sensitive cells. At the same time, a strong decrease in the ESR signal of semiquinone type with a g-factor of 2.006 was observed in a culture of resistant cells grown in the absence of doxorubicin as compared with sensitive cells grown under similar conditions. At the same time, a decrease in the level of paramagnetic nitrosyl complexes of nonheme iron in resistant cells was recorded, indicating a decrease in the content of free nonheme iron as a result of the formation of drug resistance. In addition, a decrease in the level of mRNA of the transferrin receptor in resistant cells was found by the RT-PCR. These data indicate the development of a coodinated redox-dependent adaptive response, which makes itself evident as a suppression of free radical processes during the formation of resistance of K562 cells to doxorubicin.
AuthorsA N Saprin, E V Kalinina, V A Serezhenkov, Ia N Kotova, V S Solomka, N P Shcherbak
JournalBiofizika (Biofizika) 2006 May-Jun Vol. 51 Issue 3 Pg. 485-90 ISSN: 0006-3029 [Print] Russia (Federation)
PMID16808348 (Publication Type: English Abstract, Journal Article)
Chemical References
  • Antibiotics, Antineoplastic
  • Nitrogen Oxides
  • RNA, Messenger
  • Receptors, Transferrin
  • Superoxides
  • dinitrosyl iron complex
  • Doxorubicin
  • Iron
Topics
  • Antibiotics, Antineoplastic (pharmacology)
  • Doxorubicin (pharmacology)
  • Drug Resistance, Neoplasm
  • Electron Spin Resonance Spectroscopy
  • Humans
  • Iron (metabolism)
  • K562 Cells
  • Nitrogen Oxides (metabolism)
  • Oxidation-Reduction
  • RNA, Messenger (biosynthesis)
  • Receptors, Transferrin (biosynthesis, genetics)
  • Reverse Transcriptase Polymerase Chain Reaction
  • Superoxides (metabolism)

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