The quantitative and qualitative analyses of clustered DNA damage for its radiobiological impact

Abstract

Clustered DNA damage is densely accumulation of multiple damage localized to the limited region of DNA strand passed through by the beam of ionizing radiation. Since clustered DNA damage is thought to inhibit DNA replication and resist repair activity strongly, we consider that clustered DNA damage is one of major factor deciding the singularity of radiation effect. To confirm this idea, we analyzed the yields of clustered DNA damage in the isolated DNA molecule and the chromosomal DNA in Chinese Hamster Overy cell irradiated with gamma-rays (0.2 keV/μm) and various accelerated ion particle beams including carbon (13 keV/μm), silicon (55 keV/μm), and iron ions (200 keV/μm). Although simultaneous cell surviving tests showed LET-dependent argumentation of the severity, the yields of clustered DNA damage decreased in the irradiated isolated DNA and chromosomal DNA in the irradiated cells with an increase in LET (J. Radiat. Res., 49: 133-136, 2008). The results with these biochemical and intracellular studies suggest that the quantitative factor of clustered DNA damage is not important to the effect of higher LET-radiation. On the other hand, such conventional procedures to analyze clustered DNA damage cannot demonstrate the qualitative aspect of clustered DNA damage. We here refer to our ongoing experimental design to analyze the quality of clustered DNA damage and discuss the implication of clustered DNA damage with radiation effect.