Attenuation of acridine mutagen ICR-191--DNA interactions and DNA damage by the mutagen interceptor chlorophyllin.
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.
Pietrzak
Monika
M
Department of Physics and Biophysics, University of Warmia and Mazury in Olsztyn, Oczapowskiego 4, 10-719 Olsztyn, Poland.
Halicka
H Dorota
HD
Wieczorek
Zbigniew
Z
Wieczorek
Jolanta
J
Darzynkiewicz
Zbigniew
Z
D000585:Aminacrine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000633:toxicity; D016587:Antimutagenic Agents / Q000737:chemistry / Q000494:pharmacology; D001667:Binding, Competitive / Q000187:drug effects; D018890:Chemoprevention; D002735:Chlorophyllides / Q000737:chemistry / Q000494:pharmacology*; D004247:DNA / Q000737:chemistry* / Q000187:drug effects; D004249:DNA Damage; D018922:HL-60 Cells; D006801:Humans; D046911:Macromolecular Substances / Q000737:chemistry; D009153:Mutagens / Q000737:chemistry / Q000633:toxicity*; D009588:Nitrogen Mustard Compounds / Q000737:chemistry / Q000633:toxicity*
D016587:Antimutagenic Agents; D002735:Chlorophyllides; D046911:Macromolecular Substances; D009153:Mutagens; D009588:Nitrogen Mustard Compounds; D000585:Aminacrine; D004247:DNA; C004294:acridine half-mustard; C007020:chlorophyllin