Induction of oxidative DNA damage by flavonoids of propolis: its mechanism and implication about antioxidant capacity.

Propolis from beehives is commonly used as a home remedy for various purposes including as a topical antiseptic. Despite its antioxidant capacity, propolis induces oxidative DNA damage. In exploring the underlying mechanism, we found that the induction of oxidative DNA damage is attributed to the hydrogen peroxide (H(2)O(2)) produced by propolis. The formation of H(2)O(2) can take place without the participation of cells but requires the presence of transition metal ions such as iron. Flavonoids such as galangin, chrysin, and pinocembrin that are commonly detected in propolis have the capacity to induce oxidative DNA damage, and that capacity correlates with the production of H(2)O(2), suggesting the involvement of flavonoids in propolis in this process. On the basis of these results, we propose that the flavonoids of propolis serve as temporary carriers of electrons received from transition metal ions that are relayed to oxygen molecules to subsequently generate superoxide and H(2)O(2). In addition, propolis induces oxidative DNA damage that is subject to repair, and propolis-treated cells show a lower level of DNA damage level when challenged with another oxidative agent such as amoxicillin. This is reminiscent of an adaptive response that might contribute to the beneficial effects of propolis.

Delay of gap filling during nucleotide excision repair by base excision repair: the concept of competition exemplified by the effect of propolis.

Nucleotide excision repair (NER) consists of a sequence of events including DNA damage recognition, excision of the damage containing oligonucleotide, gap filling, and ligation. We found that gap filling during the repair of ultraviolet (UV)C-induced DNA lesions was inhibited by various compounds, e.g., amoxicillin, and mixtures, e.g., propolis, the materials that could induce oxidative DNA damage in serum-supplemented cell cultures. Such inhibitory effect was also demonstrated by the immunostaining experiment and host cell reactivation assay. In this study, we link the repair of oxidative DNA damage with the inhibition of gap filling. Our experimental evidence includes the following: (1) induction of oxidative DNA damage and inhibition of gap filling were quantitatively correlated; (2) although the repair of UV-induced DNA damage was delayed in the presence of propolis, the repair of propolis-induced oxidative DNA damage proceeded regardless of preexposure to UV radiation; (3) inhibition of gap filling by propolis was absent in base excision repair (BER)-deficient cells; (4) suppression of propolis-induced oxidative DNA damage by ß-carotene abolished the inhibition of gap filling; and (5) inhibition of gap filling was also found with typical BER-inducing agents such as hydrogen peroxide, menadione, and methyl methanesulfonate. We propose that competition may occur between NER and BER, which results in delay of gap filling. Our study reveals the dominancy of BER over NER.