Designing a ridge filter based on a mouse foot skin reaction to spread out Bragg-peaks for carbon-ion radiotherapy.

Carbon-ion radiotherapy uses spread-out Bragg peaks (SOBP) to produce uniform biological effects within a target volume. The relative biological effectiveness is determined by the in vitro cell kill after a single dose is employed to design the SOBP. A question remains as to whether biological effects for in vivo tissues after fractionated doses are also uniform within the SOBP

High biological effectiveness depends on the direct action by heavy ions

The contribution of indirect action mediated by OH radicals in cell killing can be estimated from the experiment using an OH radical scavenger DMSO, which suppresses indirect action without affecting direct action. Exponentially growing Chinese hamster ovary cells under oxic and hypoxic conditions were exposed to X-rays and high-LET heavy ion radiations of 15 to 480 keV/micrometer in the presence or absence of DMSO, and their survival fractions were determined using a colony formation assay. The contribution of indirect action to cell killing decreased with increasing LET under both oxic and hypoxic conditions. The contributions under hypoxic condition were lower than that under oxic condition at each LET data point. The RBE and OER were determined at a survival level of 10%. The RBE values under both oxic and hypoxic conditions increased with LET, reached a peak at around 200 keV/micrometer, and then decreased with LET. The OER value started to decrease at around 50 keV/micrometer, and became below 2 at around 90 keV/micrometer, and then reached approximately 1 or slightly higher in the very high LET region. When the RBE and the OER were estimated separately for direct action (RBED and OERD) and indirect action (RBEI and OERI), the RBED under both conditions were larger than RBEI at 90-480 keV/micrometer. OERD was smaller than OERI at every LET data point. Thus, the direct action by heavy-ion beams gives a remarkably large RBE and small OER for cell killing in comparison to OH radical-mediated indirect action.39th Annual Meeting of the European Radiation Research Societ

INDUCTION OF DNA DSB AND ITS REJOINING IN CLAMPED AND NON-CLAMPED TUMOURS AFTER EXPOSURE TO CARBON ION BEAMS IN COMPARISON TO X RAYS

We studied DSB induction and rejoining in the clamped and non-clamped transplanted tumors in mice leg after 80 keV/µm carbon ions and X-rays. The yields of DSB in the tumors were analyzed by a static-field gel electrophoresis. The OER of DSB after X-rays was 1.68 +/- 0.31, and this value was not changed by one hour rejoining time (1.40 +/- 0.26). These damages in oxygenated conditions were rejoined 60 to 70% within one hour in situ. On the other hand, no difference between X-rays and carbon ions was found for the induction and rejoining of DSB. Thus, the values of OER and rejoined fraction after carbon ions were similar to that after X-rays, and the calculated RBEs of carbon ion were around 1 under both oxygen conditions. The yields of DSB in vivo depend on exposure doses, oxygen conditions and rejoining time, but not the types of radiation quality

Direct and Indirect Actions to High-LET Radiations

The biological effects of radiation originate principally from damages to DNA. DNA damage by photon radiation as well as heavy ions, is induced by a combination of direct and indirect actions. The contribution of indirect actions in cell killing can be estimated from the maximum degree of protection by dimethylsulfoxide (DMSO), which suppresses OH radical-mediated indirect action, without affecting the direct action. Exponentially growing Chinese hamster V79 cells were exposed to high LET radiation of 20 to 2106 keV/µm in the presence or absence of DMSO, and their survival was determined using a colony formation assay. The contribution of indirect action to cell killing decreased with increasing LET. However, the contribution did not reach zero even at very high LETs, and was estimated to be 32% at an LET of 2106 keV/µm. Therefore, even though the radiochemically estimated G value of OH radicals was nearly zero at an LET of 2000 keV/µm, indirect action by OH radicals substantially contributed to the biological effects of high LET radiations. The RBE determined at a survival level of 10% increased with LET, reaching a maximum value of 3 at around 100 keV/µm, and decreased thereafter. When the RBE was estimated separately for direct action and indirect action, the RBE resulting from indirect action had a peak at around 70 keV/µm with a gradual decrease with increasing LET. In contrast, the RBE of direct action peaked at around 200 keV/µm. Furthermore, the peak value for direct action (~6) was much higher than for indirect action (~2.5). Therefore, the direct action contributes more to the high RBE of high LET radiations than indirect action.KI-NIRS Joint Symposium on Carbon Ion Therap