**7. Conclusion**

Bioflavonoids are prevalent in the human diet from natural sources such as fruits and vegetables, but are also found at supranatural concentrations in dietary supplements and energy drinks. These chemical compounds have numerous cellular effects including interfering with signal transduction pathways, modifying the DNA damage response and epigenetic markers, and poisoning of Top2 causing DNA DSBs and leading to aberrant repair. Given the number of cellular pathways bioflavonoids affect, and the DNA damage caused by bioflavonoid exposure, it is possible that bioflavonoids could be used as natural analogs of traditional chemotherapeutic agents. However, more research is needed to understand how these bioflavonoids cause DNA damage through Top2-dependent or -independent pathways to understand potential off-target negative effects. In addition, further research will be needed to understand the dose-dependent activities of bioflavonoids and at what doses they may be chemo-protective versus what threshold doses they may induce DNA damage that is mutagenic, and finally at what high acute doses they may induce DNA damage and apoptosis to act as effective alternative to traditional chemotherapeutic agents.
