Photoinduction of strand scission in DNA by uric acid and Cu(II)

Uric acid (2,6,8-trioxo purine) is produced in mammalian systems as an end product of purine metabolism and has been proposed as a natural, physiological antioxidant. In the presence of Cu(II) and molecular oxygen, uric acid caused breakage of calf thymus DNA and supercoiled plasmid DNA. Such breakage was considerably enhanced in the presence of visible light. The DNA cleavage did not appear to have any preferred site(s) or sequence(s) for strand scission. Uric acid catalyzed the reduction of Cu(II) to Cu(I), which was shown to be an essential intermediate in the DNA cleavage reaction. Uric acid also reduced oxygen to superoxide, and hydroxyl radicals were formed in the presence of Cu(II). The involvement of active oxygen species in the reaction was established by the inhibition of DNA breakage by known scavengers of oxygen radicals.