Effect of Oxygen and Nitroaromatic Cell Radiosensitizers on Radiation-Induced Cleavage of Internucleotide Bonds: ApA, dApA, and poly(A)

Irradiation of the dinucleoside monophosphates ApA and dApA in deoxygenated solution leads to a preferential cleavage of the 3′ end of the internucleotide bond. Cleavage at the 3′ bond is favored to the extent of 2 to 1 over 5′ cleavage. Oxygen and nitroaromatic compounds inhibit 3′ bond breaking in ApA and dApA in agreement with earlier findings from studies of 3′- and 5′-mononucleotides. In contrast to the mononucleotide results, no enhancement of 5′ cleavage is observed for ApA and dApA irradiated in the presence of oxygen or the nitroaromatic additives. The over-all effect of the additives is to decrease the combined (3′ and 5′) yield of internucleotide bond breaking in ApA and dApA. This phenomenon is also observed for polyadenylic acid in the presence of the nitroaromatics. Oxygen marginally enhances internucleotide bond breaking in polyadenylic acid (factor 1.1) over that seen in deoxygenated solution. Postirradiation alkaline hydrolysis of dApA leads to further ester cleavage revealing the presence of radiation-induced alkali-labile bonds. The number of these bonds decreases in the order oxygen > nitrofurans > nitrobenzenes ∼ irradiation in the absence of additives.