A LET-Dependent Decrease in the Apoptotic Response of Normal Human Fibroblast Cultures to Isosurvival Doses of γ-Rays and Energetic Heavy Ions

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 γ-rays. Notwithstanding, its potential impact at isosurvival doses is yet to be characterized. Here we investigated the cell-killing effectiveness of γ-rays (0.2 keV/μm) and five different beams of heavy ions with LET ranging from 16.2 to 1610 keV/μm in confluent cultures of normal human fibroblasts. The relative biological effectiveness based on the dose giving 10% clonogenic survival peaked at 108 keV/μm. 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.