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 oxy
gen, uric acid caused breakage of calf thymus DNA and supercoiled plas
mid DNA. Such breakage was considerably enhanced in the presence of vi
sible light. The DNA cleavage did not appear to have any preferred sit
e(s) or sequence(s) for strand scission. Uric acid catalyzed the reduc
tion of Cu(II) to Cu(I), which was shown to be an essential intermedia
te in the DNA cleavage reaction. Uric acid also reduced oxygen to supe
roxide, and hydroxyl radicals were formed in the presence of Cu(II). T
he involvement of active oxygen species in the reaction was establishe
d by the inhibition of DNA breakage by known scavengers of oxygen radi
cals.