Metal-mediated DNA damage is the primary cause of cell death under oxidative stress conditions, and this damage can cause neurodegenerative and cardiovascular diseases, diabetes, cancer, and aging. Antioxidants have great potential to prevent these diseases, and studies of antioxidant activity typically focus on scavenging damaging reactive oxygen species. In contrast, we have quantified and compared the abilities of widely-studied sulfur, selenium, and polyphenol antioxidants to inhibit metal-mediated DNA damage and found that metal binding, not radical scavenging, is the primary mechanism for their DNA damage prevention activity.  All three classes of antioxidants prevent DNA damage by coordinating the iron and copper ions responsible for hydroxyl radical generation.  From these studies, we have developed the first predictive models for polyphenol DNA damage and cell death prevention based on iron binding. This innovative and general antioxidant mechanism highlights the critical role of metal coordination in the development of antioxidant supplements and therapies.

Metals matter: Antioxidant prevention of DNA damage and cell death

247th National Meeting (2014)

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