Abstract
[Background and Purpose] The fractionated irradiation is standard protocol for radiotherapy including carbon-ion therapy. There are big differences between single and fractionation, for example on DNA damage repair, reoxygenation of hypoxic region, etc. It is necessary to get the results using fractionated irradiation to know the effects in clinical. The purpose of this study is to examine the effects of fractionated irradiation for metastasis using C-ions and X-rays. [Materials and Methods] A mouse osteosarcoma cells, LM8 were used. All irradiation were performed with C-ions at the center of 6cm-SOBP and X-rays as reference beam. in vitro: The cytotoxic effects were examined using colony formation assay, and the inhibit effects of migration and invasion were examined using Boyden chamber assay and Matrigel invasion assay, respectively. in vivo: LM8 tumors inoculated into right hind leg of mice were irradiated. Radiosensitivity for whole tumors was obtained by tumor growth curves and for individual cell in a tumor was obtained by in vivo-in vitro assay. The metastatic effects were analyzed with the spontaneous lung metastasis model. [Results] in vitro: After fractionated irradiation, cell survival, migration and invasion activity were enhanced with the increment of fraction number. The degree of enhancement was more significant after X-rays than C-ions. in vivo: Anti-tumor effects were decreased and the number of lung metastatic nodules were increased depend on the fraction number. These effects were also more remarkable by X-rays than C-ions. [Conclusion] It is confirmed that the anti-metastatic effects after fractionated irradiation were decreased compared with single irradiation, however the degree was more smaller for C-ions with high LETs than X-rays with low LETs. It was suggested that carbon ion therapy was superior to photon therapy to suppress the metastasis even for clinical fractionated irradiation.
