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Report No.
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"${it In vitro}$" DNA protective properties of Silybin and analogues against X-ray radiation

Fu, H.*; Lin, M.; Hata, Kuniki ; Muroya, Yusa*; Fujii, Kentaro; Katsumura, Yosuke; Yokoya, Akinari; Shikazono, Naoya; Hatano, Yoshihiko

Natural flavonoids such as silybin (SLB) are believed to be active constituents of plants accounting for the reported chemoprevention of certain cancers. However, molecular mechanisms by which the low-concentration SLB and analogues in human can reduce the incidence are not clear. Using an ${it in vitro}$ plasmid DNA system with radiolytically generated reactive oxygen species (ROS) under constant scavenging conditions, it was shown that the tested flavonoids can ameliorate free radical damage sustained by DNA. The dose modifying factor for 0.1 mM SLB for 50% protection of plasmid DNA was found to be 8.9. SLB was the most active among the tested flavonoids, with effects seen at $$mu$$M. Combined fast-reaction chemistry studies support a mechanism of electron transfer (or H-atom transfer) from SLB to ROS-induced radical sites on DNA. These results support an antioxidant role for SLB and analogues in the direct interaction with DNA radicals.

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