Inflammation Research

, Volume 64, Issue 3–4, pp 193–203 | Cite as

Methotrexate induced apoptotic and necrotic chromatin changes in rat myeloid leukemia cells

  • Gyorgy Trencsenyi
  • Fruzsina Bako
  • Gabor Nagy
  • Pal Kertai
  • Gaspar Banfalvi
Original Research Paper



It was tested as to why low-dose methotrexate (MTX) effective against rheumatoid arthritis poses considerable health risk at higher doses.


The tumorigenic potential of My1/De blast cells was followed by cytology and by the kinetics of 18FDG uptake. The toxicity of MTX on chromatin condensation was compared to predictive normal intermediates of chromosome condensation in control cells.


MTX below 0.1 µg/ml did not cause visible changes in interphase chromatin structure. At its lowest toxic concentration (0.1 µg/ml) chromatin margination was confined to the outer edge of the nucleus. Between 0.1 and 5 µg/ml concentrations apoptotic chromatin shrinkage correlated with the dose of MTX. Apoptosis was exerted in early S phase excluding the mitotic effect. At higher MTX concentrations (>10 µg/ml) necrotic disruption and expansion took place. The lowest necrotic concentration (10 µg/ml) was close to highest apoptotic MTX concentration (5 µg/ml).


The switch from apoptosis to inflammatory necrosis taking place within a narrow concentration range supports the notion of a narrow therapeutic spectrum. Chromatin changes are early markers of genotoxicity at much lower concentrations than citogenetic changes in properly chosen sensitive cells.


Leukemia Cell death Reversible permeabilization Fluorescence microscopy Chromatin structure 



This work was supported by Hungarian Scientific Research Fund (OTKA grant) T42762 grant to G.B.


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Copyright information

© Springer Basel 2015

Authors and Affiliations

  • Gyorgy Trencsenyi
    • 1
  • Fruzsina Bako
    • 1
  • Gabor Nagy
    • 2
  • Pal Kertai
    • 3
  • Gaspar Banfalvi
    • 2
  1. 1.Department of Nuclear MedicineUniversity of DebrecenDebrecenHungary
  2. 2.Department of Biotechnology and MicrobiologyUniversity of DebrecenDebrecenHungary
  3. 3.Institute of Preventive MedicineUniversity of DebrecenDebrecenHungary

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