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Attenuation of acridine mutagen ICR-191--DNA interactions and DNA damage by the mutagen interceptor chlorophyllin |
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| Authors: | Pietrzak Monika Halicka H Dorota Wieczorek Zbigniew Wieczorek Jolanta Darzynkiewicz Zbigniew |
| Affiliation: | aDepartment of Physics and Biophysics, University of Warmia and Mazury in Olsztyn, Oczapowskiego 4, 10-719 Olsztyn, Poland bBrander Cancer Research Institute at New York Medical College, Valhalla, NY, 10595, USA cDepartment of Commodities and Food Research, University of Warmia and Mazury in Olsztyn, Cieszyński Square 1, 10-726 Olsztyn, Poland |
| 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 (γH2AX), particularly in DNA replicating cells, this increase was totally abolished in the cells treated with ICR-191 in the presence of CHL. |
| Keywords: | Chlorophyllin DNA damage Histone H2AX phosphorylation Mutagen interceptor Intercalation Competitive interactions |
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