Attenuation of acridine mutagen ICR-191--DNA interactions and DNA damage by the mutagen interceptor chlorophyllin

Biophys Chem. 2008 Jun;135(1-3):69-75. doi: 10.1016/j.bpc.2008.03.004. Epub 2008 Mar 30.

Abstract

We have investigated the ability of chlorophyllin (CHL) to interact with acridine mutagen ICR-191 (2-methoxy-6-chloro-9-(3-(2-chloroethyl)aminopropylamino)acridine) and also its ability to decrease binding of ICR-191 to DNA in a simple three-component competition system: CHL-ICR-DNA. Our data indicate a strong association of ICR-191 with CHL, stronger even than the association of ICR-191 with DNA. Calculations based on the measured affinity data show that a two- to three-fold excess of CHL reduces by about two-fold the concentration of the mutagen-DNA complex. We also exposed human leukemic HL-60 cells to ICR-191 in the absence and presence of CHL and measured the mutagen-induced DNA damage. The extent of DNA damage was assessed by analysis of histone H2AX phosphorylation. While ICR-191 induced significant increase in expression of phosphorylated H2AX (gammaH2AX), particularly in DNA replicating cells, this increase was totally abolished in the cells treated with ICR-191 in the presence of CHL.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aminacrine / analogs & derivatives*
  • Aminacrine / chemistry
  • Aminacrine / toxicity
  • Antimutagenic Agents / chemistry
  • Antimutagenic Agents / pharmacology
  • Binding, Competitive / drug effects
  • Chemoprevention
  • Chlorophyllides / chemistry
  • Chlorophyllides / pharmacology*
  • DNA / chemistry*
  • DNA / drug effects
  • DNA Damage*
  • HL-60 Cells
  • Humans
  • Macromolecular Substances / chemistry
  • Mutagens / chemistry
  • Mutagens / toxicity*
  • Nitrogen Mustard Compounds / chemistry
  • Nitrogen Mustard Compounds / toxicity*

Substances

  • Antimutagenic Agents
  • Chlorophyllides
  • Macromolecular Substances
  • Mutagens
  • Nitrogen Mustard Compounds
  • Aminacrine
  • DNA
  • acridine half-mustard
  • chlorophyllin