Abstract
The purpose of present study is to clarify experimentally significance of tumor heterogeneity. Two sarcomas of # 6107 and #9037 were transplanted into syngeneic C3H male mice. Single cell suspensions for each tumor were mixed together at various ratios just prior to transplantation. When tumors grew to reach 7.5-8.0 mm in diameter, leg tumors were locally irradiated with 290 MeV/n carbon ions at an LET of 74 keV/microm that were accelerated by HIMAC synchrotron in our institute. Tumor growth (TG) time was obtained by calculating days required for a tumor to reach 5 times initial volume, and Tumor Growth Delay time was used to obtain an isoeffect dose. RBE values were calculated by comparing isoeffect doses between carbon ions and reference Cs-137 gamma rays. Tumor control probabilities were calculated by counting number of mice free of tumors 150 days after irradiation. Tumors with different ratios of mixture (RM) showed various TG time such that TG times of 8.3, 3.8 and 6.1 days were for tumors with ratios of 9:1, 5:5 and 1:9 (#6107: #9073), respectively. Isoeffect doses for 5 tumors with different RM were ranging from 18 to 48 Gy for gamma rays, and from 8 to 18 Gy for carbon ions. A tumor with RM of 9:1 showed the largest isoeffect gamma-ray dose, and was more resistant than the either parental tumors of #6107 or #9073 tumors. However, the tumor with RM of 9:1 was modest radiosensitive to carbon ions. Conditional data of tumor control probabilities showed that a tumor with RM of 9:1 was more sensitive than tumors with RM of 1:9 after carbon-ion irradiation. Possible reasons for this interaction are either hypoxic c ell fraction or G1 cell cycle phase. Factor(s) and/or signaling responsible to the interaction are unknown. It is concluded that tumor heterogeneity strongly influences RBE of high LET radiation.
