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Late-arising loss of clonogenicity in the progeny of cells surviving high- and low-LET ionizing radiations

Hamada, Nobuyuki*; Wada, Seiichi*; Funayama, Tomoo; Sakashita, Tetsuya; Kakizaki, Takehiko; Ni, M.*; Kobayashi, Yasuhiko

There is increasing evidence that ionizing radiation persistently perturbs genomic stability and induce delayed reproductive death in the descendents of survivors, however, dependence of these inductions upon linear energy transfer (LET) is still largely unknown. We have examined the cell killing effectiveness of $$gamma$$-rays (0.2 keV/$$mu$$m) and six different beams of heavy ion particles with LET values wide-ranging from 16.2 to 1610 keV/$$mu$$m in primary normal human diploid foreskin fibroblasts. First, irradiated confluent density-inhibited cultures were subjected to primary colony formation, revealing that relative biological effectiveness (RBE) based on the primary 10% survival dose peaked at 108 keV/$$mu$$m, and that inactivation cross section increased proportionally up to 437 keV/$$mu$$m. Secondly, cells harvested from primary colonies further underwent 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/$$mu$$m, very little difference between LET was observed in the RBE based on the secondary survival at 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 upon initial damages having being fixed during primary colony formation.

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