Clofibrate enhances the DNA damaging action and cytotoxicity of nitrosoureas

Terence Lawson, Peter R. Gwilt

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

The ability of N-ethyl-N-nitrosourea (ENU) to produce single strand breaks (SSB) and N,N′-bis(2-chloroethyl)-N-nitrosourea (BCNU) to produce SSB and DNA-DNA interstrand cross-links was measured in L1210 cells that had been pretreated with clofibrate (CLO). When ENU was used the SSB frequency rose from 12.4 ± 1.6 106 bases in control cells to 17.3 ± 1.5 106 bases in CLO-treated cells and from 2.8 ± 0.1 106 bases in control cells to 5.5 ± 0.4 106 in CLO-treated cells when BCNU was the damaging agent. Similarly the cross-linking frequency rose from 3.5 ± 0.1 106 bases in control cells to 12.1 ± 0.5 106 bases in CLO-treated cells when BCNU was the cross-linking agent. CLO treatment increased the production of superoxide anion four-fold over the controls and it increased the cytotoxicity of BCNU. Forty-two percent of the control + BCNU cells survived after 24 h whereas only 24% of the CLO + BCNU cells survived. The stimulation of the diffuse condition known as oxidative stress increased the interaction of nitrosoureas with DNA and resulted in increased biological responses, e.g. cytotoxicity.

Original languageEnglish (US)
Pages (from-to)119-122
Number of pages4
JournalCancer Letters
Volume70
Issue number1-2
DOIs
StatePublished - Jun 15 1993

Keywords

  • DNA damage
  • DNA-DNA cross-links
  • nitrosourea
  • oxidative stress

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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