title: Contributions of direct and indirect actions in cell killing by high-LET radiations.
abstract: The biological effects of radiation originate principally in damages to DNA. DNA damages by X rays as well as heavy ions are induced by a combination of direct and indirect actions. The contribution of indirect action in cell killing can be estimated from the maximum degree of protection by dimethylsulfoxide (DMSO), which suppresses indirect action without affecting direct action. Exponentially growing Chinese hamster V79 cells were exposed to high-LET radiations of 20 to 2106 keV/mum 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/mum. Therefore, even though the radiochemically estimated G value of OH radicals was nearly zero at an LET of 1000 keV/mum, indirect action by OH radicals contributed to a substantial fraction of the biological effects of high-LET radiations. The RBE determined at a survival level of 10% increased with LET, reaching a maximum value of 2.88 at 200 keV/mum, and decreased thereafter. When the RBE was estimated separately for direct action (RBE(D)) and indirect action (RBE(I)); both exhibited an LET dependence similar to that of the RBE, peaking at 200 keV/mum. However, the peak value was much higher for RBE(D) (5.99) than RBE(I) (1.89). Thus direct action contributes more to the high RBE of high-LET radiations than indirect action does.
authors.affiliation: Heavy-ion Radiobiology Research Group, Research Center for Charged Particle Therapy, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555, Japan. hirayama@nirs.go.jp
authors.forename: Ryoichi
authors.initials: R
authors.lastname: Hirayama
authors.forename: Atsushi
authors.initials: A
authors.lastname: Ito
authors.forename: Masanori
authors.initials: M
authors.lastname: Tomita
authors.forename: Teruyo
authors.initials: T
authors.lastname: Tsukada
authors.forename: Fumio
authors.initials: F
authors.lastname: Yatagai
authors.forename: Miho
authors.initials: M
authors.lastname: Noguchi
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Matsumoto
authors.forename: Yuki
authors.initials: Y
authors.lastname: Kase
authors.forename: Koichi
authors.initials: K
authors.lastname: Ando
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Okayasu
authors.forename: Yoshiya
authors.initials: Y
authors.lastname: Furusawa
mesh_terms: D000818:Animals; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D011839:Radiation, Ionizing