Cell death due to ACNU-induced DNA fragmentation: Inhibition by cycloheximide

Tomoko Kobayashi, Teiji Tominaga, Takashi Yoshimoto

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)

Abstract

Several anticancer drugs have recently been shown to induce cell death in a manner similar to programmed cell death or apoptosis. The purpose of this study is to explore the mode of cell death caused by ACNU, a water-soluble nitrosourea. Exposure of rat glioma cell line KEG-1 to ACNU for 2 hours resulted in oligonucleosomal DNA fragmentation, creating a 'ladder' on agarose gel electrophoresis. DNA fragmentation began 18 hours after ACNU treatment, and preceded loss of membrane integrity as evaluated by the trypan blue exclusion test. The extent of DNA fragmentation increased in a dose-dependent manner, and the cell survival rate decreased reciprocally. A translational inhibitor, cycloheximide, suppressed this DNA fragmentation and enhanced cell survival rate with partial inhibition of protein synthesis. However, a transcriptional inhibitor, actinomycin D, failed to inhibit DNA fragmentation or enhance cell survival. Cycloheximide-inhibitable DNA fragmentation was also found in the KEG-1 implanted in vivo rat model following the administration of ACNU. These findings suggest that ACNU induces cell death associates with DNA fragmentation and partially with protein synthesis.

Original languageEnglish
Pages (from-to)23-31
Number of pages9
JournalJournal of Neuro-Oncology
Volume22
Issue number1
DOIs
Publication statusPublished - 1994 Feb 1

Keywords

  • ACNU
  • DNA fragmentation
  • cycloheximide
  • glioma
  • programmed cell death
  • rat

ASJC Scopus subject areas

  • Oncology
  • Neurology
  • Clinical Neurology
  • Cancer Research

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