Abstract
The higher biological effect of the ionizing radiation suggests some specific character of damage induced by them. When ionizing radiation passes cell as a beam, it might produce multiple lesions gathering around the passing beam on the target DNA. This unique form of DNA damage induced by ionizing radiation is termed “clustered DNA damage”, which occurs rarely in events of other damaging agents. There have been several studies showing that clustered DNA damage more strongly inhibits DNA replication and resists DNA repair than isolated DNA damage. Thus clustered DNA damage is thought to be a major cause for the serious biological effects induced ionizing radiation. High-LET radiations such as heavy ion beams usually conduce to more severe victims than low-LET radiations like X-rays and γ-rays. This severity with high-LET radiations might be derived form its higher condensation of ionizations than low-LET ones. Also it suggests some differences of the yields and/or characters of induced clustered DNA damage between high and low LET radiations. In this study, we compared the yield and characters of clustered DNA damage induced by γ-rays, carbon ion beams and iron ion beams. The LETs were 0.2, 13, and 200keV/μm, respectively. The yield of clustered DNA damages in both purified target DNA molecules and the chromosomal DNA in irradiated CHO cells showed decreasing trends with increase of LET [γ > C > Fe]. We show the quantitative analysis of the intracellular clustered DNA damage with pulse field gel electrophoresis. We also characterize the clustered DNA damage induced by these radiations with oligonucleotide target molecules. Our results suggest that the most accountable cause of the biological effect with heavy ion beams is the quality of induced clustered DNA damage rather than its quantity.
