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

Abstract

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.

The Bystander Response to Heavy-Ion Radiation: Intercellular Signaling Between Irradiated and Non-Irradiated Cells

“…Heavy ions are more genotoxic and cytotoxic to directly irradiated cells than low-LET photons like X-rays and γ-rays (Ando and Kase, 2009;Hamada, 2009;Hamada et al, 2010;Fokas et al, 2009). The mode of heavy ion-induced cell death/inactivation includes apoptosis, necrosis, autophagy, premature senescence, accelerated differentiation, together with delayed reproductive death in the progeny of irradiated cells (Al-Jahdari et al, 2009;Blakely and Chang, 2009;Hamada et al, 2006Hamada et al, , 2008aJinno-Oue et al, 2010;Kakizaki et al, 2006Kakizaki et al, , 2007Kawamura et al, 2009;Sora et al, 2008). In addition to LET, the heavy-ion response depends on ion species or ion track structure (Tsuruoka et al, 2005(Tsuruoka et al, , 2008.…”