Average dose rate is the primary determinant of lipid peroxidation in liposome membranes exposed to pulsed electron FLASH beam

Background Lipid peroxidation, a self-propagating chain reaction that oxydates lipid molecules, contributes to harmful effects of ionizing radiation. A decrease in peroxidation at higher dose rates could play a role in the FLASH sparing effect. Purpose We explored how lipid peroxidation induced by FLASH (> 100 Gy/s) and conventional (CONV, < 0.2 Gy/s) radiation depends on lipid concentration and content of polyunsaturated fatty acids (PUFA). Additionally, we investigated the correlation between the lipid peroxidation and the main beam parameters characterizing pulsed electron beams, namely the dose per pulse (DRp) and the average dose rate (DRav). Methods We employed phosphatidylcholine (PC) liposomes as a model of biological membranes. Suspensions of liposomes containing different proportions of linoleic acid (LA) were prepared at various concentrations and irradiated at FLASH and CONV dose rates. Additionally, the liposomes were exposed to beams characterized by diverse combinations of DRp and DRav. The extent of lipid peroxidation was assessed by monitoring oxygen consumption (ΔpO2) and measuring the yield of malondialdehyde (MDA), and in certain instances, of lipid peroxides (LOOH). Results Regardless of the radiation dose, liposome concentration or LA content, ΔpO2 and the yield of MDA were significantly lower for FLASH than for CONV irradiation. Increase in the proportion of readily oxidizable LA in the lipid had negative effect on the MDA yield but correlated positively with ΔpO2 and LOOH yield. Exposing liposomes to beams operating at different pulse repetition frequencies, while keeping the total dose and DRp constant, resulted in markedly different ΔpO2 and MDA yields. In contrast, DRav was found to exhibit stable correlation with both MDA yield and ΔpO2. Conclusions Irradiation at FLASH dose rates produces lower yield of lipid peroxidation in PUFA-containing artificial PC membranes than CONV irradiation under all tested conditions. Time-averaged dose rate, in contrast to pulse dose rate, was the critical parameter determining the level of lipid peroxidation induced by pulsed electron beams.