Abstract
Ionizing radiation generates isolated and clustered damage in DNA. Among them, bistranded clustered damage that contains multiple oxidized bases and strand breaks on opposite strands within a few helical turns is suggested to be responsible for major deleterious biological consequences. In the present study, we quantified bistranded clustered DNA damage induced by low- and high-LET radiations. pDEL19 DNA and lambda DNA were irradiated in Tris buffer by Fe ions (LET = 200 keV/um), C ions (13 keV/um) ions, and gamma-rays (0.2 keV/um). The yield (site/bp/Gy) of bistranded clustered damage (double-strand breaks and clustered purine and pyrimidine lesions) was decreased with the increase in the LET of radiations. This result is in contrast to the high biological effectiveness (RBE) of Fe and C ions relative to that of gamma-rays, suggesting crucial roles of complex damage clusters that could not be revealed in the present analysis and the error prone repair of these clusters in cells. We also assessed the repair efficiency of clustered base damage by human DNA glycosylases using defined oligonucleotide substrates. Detailed results will also be presented in the meeting.
