Radiolysis of the Double-Stranded Polynucleotides Poly(A + U) and DNA in the Presence of Oxygen

LET Dependence of 8-Hydroxy-2′-deoxyguanosine (8-OHdG) Generation in Mammalian Cells under Air-Saturated and Hypoxic Conditions: A Possible Experimental Approach to the Mechanism of the Decreasing Oxygen Effect in the High-LET Region

“…In addition, for doublestranded oligonucleotides, the value of 3.4 was nearly similar to our results (24,37). The different reaction pathways of OH radical adduct of DNA with surrounding molecules in different environments have been discussed (24,38). It should be added that these previous studies employed 60 Co c radiation, an LET of which is 0.2 keV/lm (39), with more uniform spatial distribution of energy deposition, compared with our X-ray source with an LET of about 6 keV/lm.…”

“…In addition to the pathway from 8-OH-G, the direct pathway from double-stranded oligonucleotides via pyrimidine peroxy radical also requires oxygen as mentioned in the introduction (24), which strongly suggests the significant role of oxygen in the 8-OHdG generation in cellular environment. In support with this explanation, the reaction of DNA-OH radical adduct with oxygen is largely different between single-stranded or denatured DNA and double-stranded DNA (38). The authors found smaller yield of DNA peroxy adduct in double-stranded DNA, which may cause remarkable effect of oxygen, if produced inside DNA structure rather than spatially evenly distributed oxygen.…”

“…In favor of the second possibility, there have been several reports to raise a problem that OH radical reactions with DNA or its components are strongly dependent on the molecular environment (24,38). In the case of dG, the major reaction pathway of OH radicals with dG is the guanyl radical G(-H) formation with less contribution of the direct addition of OH radicals to dG, which leads to the formation of 8-OH-G, a precursor of 8-OHdG (24), but in the case of doublestranded oligonucleotide, which is closer to the cellular DNA situation, 8-OH-G is formed mainly via guanine cation radical followed by hydration reaction, not via guanyl radical (24,35).…”