Endonuclease activity and induction of DNA fragmentation in human myelogenous leukemic cell lines

Anticancer Res. Mar-Apr 1995;15(2):259-65.

Abstract

When four human myelogenous leukemic cell lines (HL-60, ML-1, U-937, THP-1) were exposed to either ascorbic acid, hydrogen peroxide, etoposide, tumor necrosis factor, hyperthermia or UV irradiation, their growth inhibition and oligonucleosome-size DNA fragmentation were induced. Non-myelogenous leukemic cell lines (MOLT-4, K-562) were similarly sensitive to ascorbic acid and hydrogen peroxide, but relatively resistant to etoposide, TNF, hyperthermia and UV irradiation. Furthermore, these treatments except for UV irradiation, did not induce any apparent DNA fragmentation in MOLT-4 and K-562 cells. An autodigestion experiment revealed that all of these six cell lines contained divalent cation-independent endonuclease activity as a major endonuclease. The ability of this endonuclease to produce oligonucleosome-size DNA fragmentation was stimulated at acidic, but not at neutral pH. Since this enzyme activity was not detected in the lysosomal enzyme-free nuclei, prepared from all six cell lines, the cytoplasmic localization of this enzyme was suggested. The results suggest that the endonuclease activity might be differently regulated between myelogenous and non-myelogenous leukemic cell lines.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects
  • Ascorbic Acid / pharmacology
  • Cations, Divalent / pharmacology
  • DNA Damage*
  • DNA, Neoplasm / drug effects*
  • DNA, Neoplasm / radiation effects
  • Endodeoxyribonucleases / metabolism*
  • Enzyme Induction / drug effects
  • Enzyme Induction / radiation effects
  • Etoposide / pharmacology
  • Hot Temperature
  • Hydrogen Peroxide / pharmacology
  • Hydrogen-Ion Concentration
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / enzymology
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / pathology
  • Leukemia, Myeloid / enzymology
  • Leukemia, Myeloid / pathology*
  • Lysosomes / enzymology
  • Neoplasm Proteins / metabolism*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / enzymology
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / pathology
  • Recombinant Proteins / pharmacology
  • Tumor Cells, Cultured / drug effects
  • Tumor Cells, Cultured / radiation effects
  • Tumor Necrosis Factor-alpha / pharmacology
  • Ultraviolet Rays

Substances

  • Cations, Divalent
  • DNA, Neoplasm
  • Neoplasm Proteins
  • Recombinant Proteins
  • Tumor Necrosis Factor-alpha
  • Etoposide
  • Hydrogen Peroxide
  • Endodeoxyribonucleases
  • Ascorbic Acid