DNA Strand Break Induction and Enhanced Cytotoxicity of Propyl Gallate in the Presence of Copper(II)

The antioxidant propyl gallate (PG) induced single strand breaks in PM2 DNA at concentrations higher than 0.25 μM when it was combined with copper concentrations at 5 μM and above. In combination with 100 μM CuCl 2, extensive double strand breakage was also observed. Neither PG alone nor CuCl 2 show...

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Bibliographic Details
Published in:	Free radical biology & medicine Vol. 24; no. 6; pp. 972 - 978
Main Authors:	Jacobi, Heike, Eicke, Britta, Witte, Irene
Format:	Journal Article
Language:	English
Published:	United States Elsevier Inc 01-04-1998
Subjects:	3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide Catalase - pharmacology Cell Line concentration causing a 10% inhibitory effect Copper Copper - toxicity Corticoviridae - genetics Cytotoxicity DNA Damage DNA Fragmentation - drug effects DNA strand breaks double strand break Drug Synergism dsb Fibroblasts Free radical Genotoxicity Human fibroblasts Humans Hydrogen Peroxide - adverse effects Hydrogen Peroxide - metabolism IC 10 MTT Phenanthrolines - pharmacology Propyl gallate Propyl Gallate - toxicity Reactive Oxygen Species ROS single strand break ssb ssb IC 10 Genotoxicity Cytotoxicity Human fibroblasts Propyl gallate MTT Free radical dsb PG ROS Copper DNA strand breaks
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Summary:	The antioxidant propyl gallate (PG) induced single strand breaks in PM2 DNA at concentrations higher than 0.25 μM when it was combined with copper concentrations at 5 μM and above. In combination with 100 μM CuCl 2, extensive double strand breakage was also observed. Neither PG alone nor CuCl 2 showed any strand breaking properties. DNA strand breakage was inhibited by addition of catalase or the Cu(I) chelator neocuproine, indicating the involvement of H 2O 2 and a Cu(II)/Cu(I) redox cycle in the DNA damage. DNA damage of PG/Cu(II) was also observed in human fibroblasts. Using the alkaline elution technique concentrations of 0.15–0.5 mM PG induced DNA strand breaks in combination with 2.5 mM CuCl 2, while the single substances did not show any effect. At these concentrations cell viability measured by the MTT assay was not reduced by more than 10%; however, cell growth was inhibited by PG in combination with Cu(II). This growth inhibition was apparently due to the DNA damage incurred by PG/Cu(II). The synergistic interaction between PG and Cu(II) is probably caused by a redox reaction between both compounds, whereby reactive species such as ROS are formed, which are responsible for the observed genotoxic and cytotoxic effects. Our results demonstrate that the antioxidative and cytoprotective properties of propyl gallate may change to prooxidative, cytotoxic and genotoxic properties in the presence of Cu(II).
ISSN:	0891-5849 1873-4596
DOI:	10.1016/S0891-5849(97)00400-0