Synergistic cell-killing effect of a combination of hyperthermia and heavy ion beam irradiation: In expectation of a breakthrough in the treatment of refractory cancers (Review)

We studied the sensitivity against heavy ion beam and hyperthermia on radioresistant procaryote, Deinococcus radiodurans, for the purpose of cancer therapy. First, we examined the decrease of the survival rate and molecular weight of DNA purified from this cell by acid heat treatment. These decreases were recognized by heating at 55°C below pH 5.0. Then, we assumed that the decrease in survival of D. radiodurans in vivo and damage to its DNA in vitro by acid heating were due to the release of purine rings from the phosphodiester backbone of DNA molecules, i.e., depurination. Second, we investigated the relation between LET (linear energy transfer) and RBE (relative biological effectiveness) on D. radiodurans dry and wet cells using AVF cyclotron at the TIARA facility of JAERI-Takasaki, Japan. These cells were irradiated with carbon (12C5+) ion beam at LET of about 100 keV/μm, neon (20Ne8+) ion beam at LET of about 300 keV/μm and oxygen (16O6+) ion beam at LET of about 400 keV/μm. The peak in the figure of the relation between LET and RBE value was found to increase according to the increase of LET value from 100 keV/μm. Third, we conducted combination treatment with 4.8 kGy of α-particles, i.e., boron 10 neutron captured beam induced by Kyoto University Research Nuclear Reactor operated at 5 MW, and hyperthermia at 52°C, which caused the synergistic killing effect on D. radiodurans wet cells. However, being dissimilar to the case of γ-irradiation, the interval incubation at 30°C in the medium between both treatments could inhibit the recovery of survival.