Selenite Induction of DNA Strand Breaks and Apoptosis in Mouse Leukemic L1210 Cells

Biochem Pharmacol. 1994 Apr 29;47(9):1531-5. doi: 10.1016/0006-2952(94)90528-2.

Abstract

The effects of selenite on DNA integrity, cell viability, and long-term proliferative potential of mouse leukemic L1210 cells were examined in this study. Selenite treatment resulted in concentration-dependent increases in DNA single-strand breaks and double-strand breaks, as detected by a modified filter elution assay. A time-course experiment showed that DNA single-strand breaks preceded DNA double-strand breaks. Agarose gel electrophoresis of DNA extracted from selenite-treated cells displayed a nucleosomal fragmentation pattern that is characteristic of apoptotic cell death. The involvement of a Ca2+,Mg(2+)-dependent endonuclease responsible for DNA double-strand fragmentation was implied by the observation that two inhibitors of endonuclease activity, i.e. aurintricarboxylic acid and zinc, blocked selenite-induced DNA double-strand breaks. These inhibitors also prevented selenite-induced cell death as defined by loss of ability to exclude trypan blue dye. Selenite treatment severely impaired the colony-forming ability of cells capable of trypan blue exclusion. The induction of DNA strand breaks and commitment to apoptosis may explain the selenite-mediated growth inhibition and loss of long-term proliferative potential.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Apoptosis*
  • Aurintricarboxylic Acid / pharmacology
  • Cell Survival
  • Colony-Forming Units Assay
  • DNA Damage*
  • DNA, Single-Stranded / drug effects
  • DNA, Single-Stranded / ultrastructure
  • Endonucleases / antagonists & inhibitors
  • Leukemia L1210
  • Mice
  • Selenium / analysis
  • Sodium Selenite / pharmacology*
  • Sulfates / pharmacology
  • Tumor Cells, Cultured
  • Zinc Compounds / pharmacology
  • Zinc Sulfate

Substances

  • DNA, Single-Stranded
  • Sulfates
  • Zinc Compounds
  • Aurintricarboxylic Acid
  • Zinc Sulfate
  • Endonucleases
  • Selenium
  • Sodium Selenite