Study on the Impact of Antioxidant on the FLASH Effect With 6 MeV X-Ray

Abstract

Purpose/Objective(s)Recent studies reported that the ultra-high dose rate (FLASH) irradiation induced less healthy tissue damages compared with conventional dose rate (CONV) irradiation, this phenomenon was referred to as the FLASH effect and the underlying mechanism remains elusive. This work aims to investigate the impact of antioxidants on the FLASH effect.Materials/MethodsBALB/c nude mice were treated with the antioxidant N-Acetylcysteine (NAC) and received whole abdominal 6 MeV X-ray FLASH (> 150 Gy/s) or CONV (0.2 Gy/s) irradiation. The prescribed doses were 16 Gy (lethal dose) and 10 Gy (non-lethal dose). EBT3 films were used to confirm the dose. Mice were sacrificed 24 h post-irradiation (pi) to study acute tissue responses or followed up to 6 weeks to look at late-stage responses and the survival probability. Whole blood count, cytokine expression, histologic analysis, and TUNEL assay of intestine were used performed.ResultsMice that received FLASH irradiation had a higher survival probability 6 weeks pi, and less acute and late-stage intestine damages compared to CONV irradiation. For mice that received FLASH irradiation, there are no statistically significant differences in whole blood count, survival probability and intestine damages between NAC treated group and the non-NAC treated group. However, for mice who received CONV irradiation, mice treated with NAC had significantly lower survival probability, more white blood cells, lymphocytes, and neutrophils compared to those not treated with NAC.Conclusion6 MeV X-ray FLASH irradiation can spare healthy tissues compared to CONV irradiation. Administration of antioxidant lead to more radiation induced damages under CONV irradiation but no statistic significant impact on the tissue response to FLASH irradiation. More (ongoing) experiments should be performed to study the role of antioxidants in the FLASH effect. Recent studies reported that the ultra-high dose rate (FLASH) irradiation induced less healthy tissue damages compared with conventional dose rate (CONV) irradiation, this phenomenon was referred to as the FLASH effect and the underlying mechanism remains elusive. This work aims to investigate the impact of antioxidants on the FLASH effect. BALB/c nude mice were treated with the antioxidant N-Acetylcysteine (NAC) and received whole abdominal 6 MeV X-ray FLASH (> 150 Gy/s) or CONV (0.2 Gy/s) irradiation. The prescribed doses were 16 Gy (lethal dose) and 10 Gy (non-lethal dose). EBT3 films were used to confirm the dose. Mice were sacrificed 24 h post-irradiation (pi) to study acute tissue responses or followed up to 6 weeks to look at late-stage responses and the survival probability. Whole blood count, cytokine expression, histologic analysis, and TUNEL assay of intestine were used performed. Mice that received FLASH irradiation had a higher survival probability 6 weeks pi, and less acute and late-stage intestine damages compared to CONV irradiation. For mice that received FLASH irradiation, there are no statistically significant differences in whole blood count, survival probability and intestine damages between NAC treated group and the non-NAC treated group. However, for mice who received CONV irradiation, mice treated with NAC had significantly lower survival probability, more white blood cells, lymphocytes, and neutrophils compared to those not treated with NAC. 6 MeV X-ray FLASH irradiation can spare healthy tissues compared to CONV irradiation. Administration of antioxidant lead to more radiation induced damages under CONV irradiation but no statistic significant impact on the tissue response to FLASH irradiation. More (ongoing) experiments should be performed to study the role of antioxidants in the FLASH effect.