title: LET-dependent survival of irradiated normal human fibroblasts and their descendents.
abstract: Evidence has accumulated showing that ionizing radiations persistently perturb genomic stability and induce delayed reproductive death in the progeny of survivors; however, the linear energy transfer (LET) dependence of these inductions has not been fully characterized. We have investigated the cell killing effectiveness of gamma rays (0.2 keV/microm) and six different beams of heavy-ion particles with LETs ranging from 16.2 to 1610 keV/microm in normal human fibroblasts. First, irradiated confluent density-inhibited cultures were plated for primary colony formation, revealing that the relative biological effectiveness (RBE) based on the primary 10% survival dose peaked at 108 keV/microm and that the inactivation cross section increased proportionally up to 437 keV/microm. Second, cells harvested from primary colonies were plated for secondary colony formation, showing that delayed reproductive death occurred in a dose-dependent fashion. While the RBE based on the secondary 80% survival dose peaked at 108 keV/microm, very little difference in LET was observed in the RBE based on secondary survival at the primary 10% survival dose. Our present results indicate that delayed reproductive death arising only during secondary colony formation is independent of LET and is more likely to be dependent on initial damages having been fixed during primary colony formation.
authors.affiliation: Department of Quantum Biology, Division of Bioregulatory Medicine, Gunma University Graduate School of Medicine, Maebashi, Gunma 371-8511, Japan.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Hamada
authors.forename: Tomoo
authors.initials: T
authors.lastname: Funayama
authors.forename: Seiichi
authors.initials: S
authors.lastname: Wada
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Sakashita
authors.forename: Takehiko
authors.initials: T
authors.lastname: Kakizaki
authors.forename: Meinan
authors.initials: M
authors.lastname: Ni
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Kobayashi
mesh_terms: D002455:Cell Division / Q000528:radiation effects*; D049109:Cell Proliferation / Q000528:radiation effects; D002470:Cell Survival / Q000528:radiation effects*; D002478:Cells, Cultured; D004307:Dose-Response Relationship, Radiation; D005347:Fibroblasts / Q000166:cytology* / Q000502:physiology / Q000528:radiation effects*; D005720:Gamma Rays; D006801:Humans; D018499:Linear Energy Transfer / Q000502:physiology* / Q000528:radiation effects; D011829:Radiation Dosage; D012062:Relative Biological Effectiveness