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 PM 2 DNA at concentrations higher than 0.25 mu M when it was combined wit h copper concentrations at 5 mu M and above. In combination with 100 m u M CuCl2, extensive double strand breakage was also observed. Neither PG alone nor CuCl2 showed any strand breaking properties. DNA strand breakage was inhibited by addition of catalase or the Cu(I) chelator n eocuproine, indicating the involvement of H2O2 and a Cu(Il)/Cu(I) redo x cycle in the DNA damage. DNA damage of PG/Cu(II) was also observed i n human fibroblasts. Using the alkaline elution technique concentratio ns of 0.15-0.5 mM PC induced DNA strand breaks in combination with 2.5 mM CuCl2, while the single substances did not show any effect. At the se concentrations cell viability measured by the MTT assay was not red uced by more than 10%; however, cell growth was inhibited by PG in com bination 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 com pounds, whereby reactive species such as ROS are formed, which are res ponsible for the observed genotoxic and cytotoxic effects. Our results demonstrate that the antioxidative and cytoprotective properties of p ropyl gallate may change to prooxidative, cytotoxic and genotoxic prop erties in the presence of Cu(II). (C) 1998 Elsevier Science Inc.