title: Exploration of "over kill effect" of high-LET Ar- and Fe-ions by evaluating the fraction of non-hit cell and interphase death.
abstract: The reason why RBE for cell killing fell to less than unity (1.0) with very high-LET heavy-ions ((40)Ar: 1,640 keV/microm; (56)Fe: 780, 1,200, 2,000 keV/microm) was explored by evaluating the fraction of non-hit cell (time-lapse observation) and cells undergoing interphase death (calculation based on our previous data). CHO cells were exposed to 4 Gy (30% survival dose) of Ar (1,640 keV/microm) or Fe-ions (2,000 keV/microm). About 20% of all cells were judged to be non-hit, and about 10% cells survived radiation damage. About 70% cells died after dividing at least once (reproductive death) or without dividing (interphase death). RBE for reproductive (RBE[R]) and interphase (RBE[I]) death showed a similar LET dependence with maximum around 200 keV/microm. In this LET region, at 30% survival level, about 10% non-survivors underwent interphase death. The corresponding value for very high-LET Fe-ions (2,000 keV/microm) was not particularly high (approximately 15%), whereas that for X-rays was less than 3%. However, reproductive death (67%) predominated over interphase death (33%) even in regard to rather severely damaged cells (1% survival level) after exposure to Fe-ions (2,000 keV/microm). These indicate that interphase death is a type of cell death characteristic for the cells exposed to high-LET radiation and is not caused by "cellular over kill effect". Both NHF37 (non-hit fraction at 37% survival) and inactivation cross-section for reproductive death (sigma[R]) began to increase when LET exceeded 100 keV/microm. The exclusion of non-hit fraction in the calculation of surviving fraction partially prevented the fall of RBE[R] when LET exceeded 200 keV/microm. On the other hand, the mean number of lethal damage per unit dose (NLD/Gy) showed the same LET-dependent pattern as RBE[R]. These suggest that the increase in non-hit fraction and sigma[R] with an increasing LET is caused by enhanced clustering of ionization and DNA damage which lowers the energy efficiency for producing damage and RBE.
authors.affiliation: Department of Medical Biophysics & Radiation Biology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
authors.forename: Parinaz
authors.initials: P
authors.lastname: Mehnati
authors.forename: Shigeko
authors.initials: S
authors.lastname: Morimoto
authors.forename: Fumio
authors.initials: F
authors.lastname: Yatagai
authors.forename: Yoshiya
authors.initials: Y
authors.lastname: Furusawa
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Kobayashi
authors.forename: Seiichi
authors.initials: S
authors.lastname: Wada
authors.forename: Tatsuaki
authors.initials: T
authors.lastname: Kanai
authors.forename: Fumio
authors.initials: F
authors.lastname: Hanaoka
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sasaki
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000528:radiation effects*; D001128:Argon; D016466:CHO Cells; D002470:Cell Survival / Q000528:radiation effects*; D006224:Cricetinae; D003412:Cricetulus; D004307:Dose-Response Relationship, Radiation; D020450:Heavy Ions; D007399:Interphase / Q000528:radiation effects*; D007477:Ions; D007501:Iron; D018499:Linear Energy Transfer / Q000502:physiology*; D011829:Radiation Dosage; D011839:Radiation, Ionizing
chemical_list: D007477:Ions; D001128:Argon; D007501:Iron