Abstract
High LET ionizing radiations show higher RBE than low LET ones. It is thought that clustered DNA damage specifically induced by high LET radiation is involved in higher RBE. Since recent study of DNA repair leads to utilization of various DNA repair enzymes, it is able to study more complex and underlying clustered DNA damage including base lesions (cluster base damage). To evaluate involvement of cluster base damage in the biological consequences of high LET radiation, we estimated amount of cluster base damage in DNA irradiated with heavy ion particles. Two species of DNA molecule, pDEL19 (~4.6 kbp) and lambda phage DNA (~46 kbp) were used as target substrates. These DNA were irradiated with gamma-rays (0.2 keV/μm), carbon (13 keV/μm) and iron ions (200 keV/μm) in 10 mM Tris-HCl (pH7.5). For detection of base lesions, the samples were digested by Escherichia coli endonuclease III for oxidative pyrimidines and E. coli Fpg or human OGG1 for oxidative purines, and subjected in gel electrophoresis and aldehyde reactive probe method. The result showed that amount of base lesions localized sparsely and in cluster decreased with increase of LET (gamma-rays > carbon > iron), like single and double strand breaks. The result indicates that not quantity but quality of cluster (base) damage is more important to elicit the biological effect of high LET radiation. Alternatively, cellular process of cluster base damage and variety of the final products of such process among different LET radiation seem to be important in the biological consequence of high LET radiation.
