@misc{oai:repo.qst.go.jp:00060536, author = {Ide, Hiroshi and Tanaka, Ruri and Nakarai, Yusuke and Teratou, Hiroaki and Furusawa, Yoshiya and 井出 博 and 田中 瑠理 and 寺東 宏明 and 古澤 佳也}, month = {Jul}, note = {During space flight astronauts are exposed to various types of radiation from sun and galactic cosmic rays, the latter of which contain high-energy charged particles such as Fe and C ions. The radiation risk to astronauts toward such high-energy charged particles has been assessed by ground-based experiments. When irradiated by ionizing radiation, DNA molecules suffer from oxidation of bases and strand breaks. The distribution of these lesions along the DNA strand may differ significantly between densely ionizing high-energy Fe and C ions and sparsely ionizing radiation like 60Co gamma-rays. Among various types of DNA damage, bistranded clustered lesions comprised of multiple oxidized bases or strand breaks on opposite strands within a few helical turns are of particular interest since they are assumed to be resistant to repair or induce faulty repair, hence resulting in cell killing and mutations. In the present study, we have analyzed isolated and clustered DNA lesions generated by high-energy Fe and C ions to elucidate the nature of DNA lesions. Plasmid DNA (pDEL19) was irradiated in 10 mM Tris buffer (pH 7.5) by Fe (500 MeV/amu) and C (290 MeV/amu) ions and 60Co gamma-rays. Single-strand breaks (SSB) and double-strand breaks (DSB) were quantified by analysis of conformational changes using agarose gel electrophoresis. For quantification of isolated and bistranded clustered base lesions, irradiated plasmid was exhaustively digested prior to agarose gel analysis by Endo III and Fpg that preferentially incise DNA at oxidative pyrimidine and purine lesions, respectively. The yield (site/Gy/nucleotide) of isolated damages (SSB and bases lesions) tended to decrease with increasing LET [gamma (0.2 keV/_m) < C (13 keV/_m) < Fe (200 keV/_m)]. The yield of DSB was decreased similarly, but that of clustered base lesions was virtually constant. As a result, the spectra of clustered damage changed in an LET-dependent manner: the fraction of clustered base lesions in total clustered damage was 39% (gamma), 66% (C), and 68% (Fe). The overall yield of clustered damage (DSB + clustered base lesions) that may be pertinent to cell killing and mutations was decreased with increasing LET [relative yield: 1 (gamma) > 0.77 (C) > 0.69 (Fe)]. This result is in contrast to the higher biological effectiveness (e.g. cell killing) of high-energy Fe and C ions than gamma-rays, suggesting a role of more complex damage clusters that cannot be distinguished by simple analysis of direct and DNA glycosylase-induced DSB., 35th COSPAR Scientific Assembly}, title = {Isolated and clustered DNA lesions induced by high-energy iron and carbon ions}, year = {2004} }