A LET-dependent decrease in the apoptotic response of normal human fibroblast cultures to isosurvival doses of -rays and energetic heavy ions

Hamada, Nobuyuki*; Ni, M.*; Funayama, Tomoo; Sakashita, Tetsuya; Sora, Sakura*; Nakano, Takashi*; Kobayashi, Yasuhiko

Biological effectiveness varies with the linear energy transfer (LET) of ionizing radiation. Plentiful evidence has been presented demonstrating that at physically equivalent doses, high-LET energetic heavy ions are more cytotoxic and genotoxic than low-LET photons like X-rays and -rays. Notwithstanding, its potential impact at isosurvival doses is yet to be characterized. Here we investigated the cell-killing effectiveness of -rays (0.2 keV/m) and five different beams of heavy ions with LET ranging from 16.2 to 1610 keV/m in confluent cultures of normal human fibroblasts. The relative biological effectiveness based on the dose giving 10% clonogenic survival peaked at 108 keV/m. In cultures exposed to the 10% survival doses, the yield of apoptotic cells escalated with time postirradiation but declined with LET. Our results imply that the cell death mode differs with LET at isosurvival levels.