Roles of vitamin C in radiation-induced DNA damage in presence and absenceof copper

Exposure to either ionizing radiation or certain transition metals results in generation of reactive oxygen species that induce DNA damage, mutation, and cancer. Vitamin C (a reactive oxygen scavenger) is considered to be a d ietary radioprotective agent. However, it has been reported to be genotoxic in the presence of certain transition metals, including copper. In order t o explore the capacity of vitamin C td protect DNA from radiation-induced d amage, and the influence of the presence of copper on this protection, we i nvestigated vitamin C-mediated protection against radiation-induced damage to calf thymus DNA in vitro in the presence or absence of copper(II). Vitam in C (0.08-8.00 mM, pH 7.0) significantly reduced DNA damage induced by gam ma -irradiation (30-150 Gy) by 30-50%, similar to the protective effect of glutathione. However, vitamin C plus copper (50 muM) significantly enhanced T-radiation- induced DNA damage. Low levels of added copper (5 muM), or ch elation of copper with 1-N-benzyltriethylenetetraine tetrahydro chloride (B zTrien) and bathocuprinedisulfonic acid (BCSA), abolished the enhanced dama ge without diminishing the protective effect of vitamin C. These results in dicate that vitamin C can act as: (1) an antioxidant to protect DNA damage from ionizing radiation; and (2) a reducing agent in the presence of copper to induce DNA damage. These effects are important in assessing the role of vitamin C, in the presence of mineral supplements or radioprotective thera peutic agents, particularly in patients with abnormally high tissue copper levels. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.