Does DSB increase or decrease with increasing LET? (2) A statement from the Decrease.

Through the whole history of radiation biology, it has been convinced that DNA double strand break (DSB) is the most important causation of radiation biological effect. After utilization of various heavy ion particle beams, there have been hundreds of studies to focus the relationship between the yields of DSB and the linear energy transfer of used radiation. However, respective results of those studies showed no uniform tendency of LET-dependent yields of DSB. Therefore, I studied simultaneous parallel processing of different procedures to resolve this problem with LET-DSB relationship mentioned above. For purified DNA molecule targets, both pDEL19, a circular plasmid DNA (4,814 bp) and linear lambda phage DNA (48,502 bp) in buffered solution (10 mM Tris-HCl, pH 7.5) were irradiated by gamma-rays, carbon ion beams and iron ion beams. The LET were 0.2, 13, and 200 keV/µm, respectively. The irradiated pDEL19 were subjected with static field gel electrophoresis and the yield of DSB were estimated by the conformational changes from intact closed circular form to DSB-related linear form. The irradiated lambda phage DNA were separated in pulse field gel electrophoresis and the yield of DSB were determined by number average molecular weight of the released bands derived from fragmentation. Intracellular DSB were estimated by FAR assay of the chromosomal DNA of irradiated cells. Our results with both irradiated purified DNA targets and irradiated cells showed that the yields of DSB decreased with the increase of the LET. I discuss the possible molecular mechanism for the LET-dependent yield of DSB with similar previous studies.