IMRT Hyper-radiosensitivity and Increased radioresistance Radiation adaptive response Radiation-induced bystander effect 0.5 Gy hyper-radiosennsitivity HRS 0.5 Gy increased radioresistance IRR HRS IRR HRS IRR 0.2 Gy HRS IRR 0.5 Gy HRS 0.5 Gy IRR DNA Gy 0.5 Gy HRS 20 1984 Wolff LQ Joiner Gy FACScan 0.5 Gy 0.5 Gy Gy LQ HRS IRR 36
0.025 Gy 0.05 0.1 Gy 2.5 0.15 0.2 Gy 0.3 0.5 Gy PKC PKC p53 PI3K p53 p53 1992 Nagasawa Little DNA p53 10 Fas Fas 11 Gy Fas Fas Mothersill Seymour 0.5 Gy irradiated conditioned medium ICM 37
12 Lehnert 8.4 cgy TNF- TGF- 1 13 14 Barcellos-Hoff TGF- 1 15 nitric oxide NO 16 17 LET LET LET LET LET NO 16 17 p53 inos NO Shao Gy LET LET X NO 18 Lehnert 19 NO HRS IRR HRS IRR HFL-1 cgy HFL-1 HFL-1 Iyer and Lehnert 2002 38
NO Spring-8 HRS IRR 1 M.C. Joiner, B. Marples, P. Lambin, et al.: Low-dose hypersensitivity: Current status and possible mechanisms, Int. J. Radiat. Oncol. Biol. Phys., 49, 379-389 2 M.C. Joiner, P. Lambin, E.P. Malaise, et al.: Hypersensitivity to very-low dose single radiation doses: Its relationship to the adaptive response and induced radioresistance, Mutat. Res., 358, 171-183 1996 3 G. Olivieri, J. Bodycote, and S. Wolff: Adaptive response of human lymphocytes to low concentrations of radioactive thymidine, Science, 223, 594-597 1984 4 L. Cai, and S.Z. Liu: Induction of cytogenetic adaptive responses of somatic and germ cells in vivo and in vitro by low dose X-irradiation, Int. J. Radiat. Biol., 58, 187-194 1990 5 M. Yonezawa, J. Misonoh, and Y. Hosokawa: Twotypes of X-ray-induced radio-resistance in mice: Presence of 4 dose ranges with distinct biological effects, Mutat. Res., 358, 237-24 1996 6 S. Wolff: The adaptive response in radiobiology: Evolving insights and implications, Environ. Health Perspect., 108, 277-283 1998 7 M.S. Sasaki: On the reaction kinetics of the radioadaptive response in cultured mouse cells, Int. J. Radiat. Biol., 68, 281-291 1995 8 A. Takahashi: Different inducibility of radiation- or heat-induced p53-dependent apoptosis after acute or chronic irradiation in human cultured squamous cell carcinoma cells, Int. J. Radiat. Biol., 77, 215-224 9 H. Nagasawa, and J.B. Little: Induction of sister chromatid exchanges by extremely low doses of alpha-particles, Cancer Res., 52, 6394-639 1992 10 E.I. Azzam, S.M. de Toledo, and J.B. Little: Direct evidence for the participation of gap junction-mediated intercellular communication in the transmission of damage signals from alpha-particle irradiated to non-irradiated cells, Proc. Natl. Acad. Sci. USA, 98, 473-478 11 J. Albanese, and N. Dainiak: Ionizing radiation alters Fas antigen ligand at the cell surface and on exfoliated plasma membrane-derived vesicles: Implications for apoptosis and intercellular signaling, Radiat. Res., 153, 49-61 2000 12 C. Mothersill, and C.B. Seymour: Cell-cell contact during gamma irradiation is not required to induce a bystander effect in normal human keratinocytes: Evidence for release during irradiation of a signal controlling survival into medium, Radiat. Res., 149, 256-262 1998 13 B.E. Lehnert, and E.H. Goodwin: Extracellular factor(s) following exposure to alpha particles can cause sister chromatid exchanges in normal human cells, Cancer Res., 57, 2164-2171 1997 14 P.K. Narayanan, E.H. Goodwin, and B.E. Lehnert: Alpha particles initiate biological production of superoxide anions and hydrogen peroxide in human cells, Cancer Res., 57, 3963-3971 1997 15 M.H. Barcellos-Hoff, and A.L. Brooks,: Extracellular signaling through the microenvironment: A hypoth- 39
esis relating carcinogenesis, bystander effects, and genomic instability, Radiat. Res., 156, 618-627 16 H. Matsumoto, S. Hayashi, M. Hatashita, et al.: Induction of radioresistance to accelerated carbonion beams in recipient cells by nitric oxide excreted from irradiated donor cells of human glioblastoma, Int. J. Radiat. Biol., 76, 1649-1657 2000 17 H. Matsumoto, S. Hayashi, M. Hatashita, et al.: Induction of radioresistance by a nitric oxide-mediated bystander effect, Radiat. Res., 155, 387-396 18 C.L. Shao, M. Aoki, and Y. Furusawa: Mediummediated bystander effects on HSG cells co-cultivated with cells irradiated by X-rays or a 290 MeV/u carbon beam, J. Radiat. Res., 42, 305-316 19 R. Iyer, and B.E. Lehnert: Alpha-particle-induced increases in the radioresistance of normal human bystander cells, Radiat. Res., 157, 3-7 2002 40