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

Gyorgy Trencsenyi, Fruzsina Bako, Gabor Nagy, Pal Kertai, G. Bánfalvi

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

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

Original languageEnglish
Pages (from-to)193-203
Number of pages11
JournalInflammation Research
Volume64
Issue number3-4
DOIs
Publication statusPublished - 2015

Fingerprint

Myeloid Leukemia
Myeloid Cells
Methotrexate
Chromatin
Poisons
Interphase
Fluorodeoxyglucose F18
S Phase
Cell Biology
Rheumatoid Arthritis
Necrosis
Chromosomes
Apoptosis
Health

Keywords

  • Cell death
  • Chromatin structure
  • Fluorescence microscopy
  • Leukemia
  • Reversible permeabilization

ASJC Scopus subject areas

  • Pharmacology
  • Immunology

Cite this

Methotrexate induced apoptotic and necrotic chromatin changes in rat myeloid leukemia cells. / Trencsenyi, Gyorgy; Bako, Fruzsina; Nagy, Gabor; Kertai, Pal; Bánfalvi, G.

In: Inflammation Research, Vol. 64, No. 3-4, 2015, p. 193-203.

Research output: Contribution to journalArticle

Trencsenyi, Gyorgy ; Bako, Fruzsina ; Nagy, Gabor ; Kertai, Pal ; Bánfalvi, G. / Methotrexate induced apoptotic and necrotic chromatin changes in rat myeloid leukemia cells. In: Inflammation Research. 2015 ; Vol. 64, No. 3-4. pp. 193-203.
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