Formation and reaction of peroxyl radicals of polynucleotides and DNA in aqueous solution

Abstract Radiation-induced strand breaks of polyuridylic acid [poly(U)] in aqueous solution in the presence of oxygen are known to proceed via peroxyl radicals of the uracil residues. The peroxyl radicals abstract H atoms from sugar moieties, and reaction of the sugar radicals leads to chain breaks. The lifetimes of the peroxyl radicals of poly(U), polyadenylic acid [poly(A)] and of single- and double-stranded DNA were determined by time-resolved e.s.r. spectroscopy and found to be in the range of seconds whereas the peroxyl radicals of low-molecular-weight model compounds have lifetimes of several milliseconds. In poly(U), the rate of decay of the peroxyl radicals was shown to coincide with the rate of strand-break formation, determined from pulse conductivity measurements. This leads to the conclusion that the reaction of peroxyl radicals with the sugar moieties is the rate-limiting step in strand-break formation. The peroxyl radicals of poly(U), poly(A) and DNA react with various thiols with rate constants of ⋍10 4 –10 5 M −1 s −1 . Strand-break formation in poly(U) was found to be prevented by thiols. The consequences of these results for the radioprotection of living cells are discussed.