Zinc ion enhances GABA tea-mediated oxidative DNA damage.

GABA tea is a tea product that contains a high level of γ-aminobutyric acid (GABA). Previous study has demonstrated a synergistic effect of GABA tea and copper ions on DNA breakage. This study further explored whether zinc (Zn), a nonredox metal, modulated DNA cleavage induced by GABA tea extract. In a cell-free system, Zn(2+) significantly enhanced GABA tea extract and (-)-epigallocatechin-3-gallate (EGCG)- or H(2)O(2)-induced DNA damage at 24 h of incubation. Additionally, low dosages of GABA tea extract (1-10 µg/mL) possessed pro-oxidant activity to increase H(2)O(2)/Zn(2+)-induced DNA cleavage in a dose-dependent profile. By use of various reactive oxygen scavengers, it was observed that glutathione, catalase, and potassium iodide effectively inhibited DNA degradation caused by the GABA tea extract/H(2)O(2)/Zn(2+) system. Moreover, the data showed that the GABA tea extract itself (0.5-5 mg/mL) could induce DNA cleavage in a long-term exposure (48 h). EGCG, but not the GABA tea extract, enhanced H(2)O(2)-induced DNA cleavage. In contrast, GABA decreased H(2)O(2)- and EGCG-induced DNA cleavage, suggesting that GABA might contribute the major effect on the antioxidant activity of GABA tea extract. Furthermore, a comet assay revealed that GABA tea extract (0.25 mg/mL) and GABA had antioxidant activity on H(2)O(2)-induced DNA breakage in human peripheral lymphocytes. Taken together, these findings indicate that GABA tea has the potential of both pro-oxidant and antioxidant. It is proposed that a balance between EGCG-induced pro-oxidation and GABA-mediated antioxidation may occur in a complex mixture of GABA tea extract.

A synergistic effect of GABA tea and copper(II) on DNA breakage in human peripheral lymphocytes.

GABA tea is a tea product that contains a high level of γ-aminobutyric acid (GABA). The oxidant and antioxidant roles of GABA tea in DNA damage were investigated in this study. DNA cleavage was observed by GABA-tea extract in the presence of copper ions. Comet assay revealed that combination of GABA-tea extract, but not pure GABA, and Cu(2+) is capable of oxidatively degrading cellular DNA in human peripheral lymphocytes. Using various reactive oxygen scavengers, we found that catalase and sodium azide effectively inhibited GABA-tea extract/Cu(II)-induced DNA degradation, suggesting the essential role of singlet oxygen and H(2)O(2) in the reaction. In addition, neocuproine inhibited the DNA degradation, confirming that Cu(I) is an intermediate in the DNA cleavage reaction. Therefore, we speculate that GABA-tea extract/Cu(II)-induced DNA damage is probably mediated through the formation of H(2)O(2) and the reduction of copper. Furthermore, our data showed that GABA-tea extract was more genotoxic and pro-oxidant than its major catechin constituent, (-)-epigallocatechin-3-gallate (EGCG), leading to DNA cleavage in the presence of Cu(2+). These findings will provide implications for the potential of GABA-tea extract in anticancer property, which may involve copper ions and the consequent pro-oxidant action.