Journal
SCIENTIFIC REPORTS
Volume 9, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/s41598-019-53562-y
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Funding
- MD Anderson Cancer Center support grant [P30 CA16672]
- John E. and Dorothy J. Harris Endowed Professorship
- NCI [P30CA016672]
- [U01CA216468]
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Recent reports have shown that very high dose rate radiation (35-100Gy/second) referred to as FLASH tends to spare the normal tissues while retaining the therapeutic effect on tumor. We undertook a series of experiments to assess if ultra-high dose rate of 35Gy/second can spare the immune system in models of radiation induced lymphopenia. We compared the tumoricidal potency of ultra-high dose rate and conventional dose rate radiation using a classical clonogenic assay in murine pancreatic cancer cell lines. We also assessed the lymphocyte sparing potential in cardiac and splenic irradiation models of lymphopenia and assessed the severity of radiation-induced gastrointestinal toxicity triggered by the two dose rate regimes in vivo. Ultra-high dose rate irradiation more potently induces clonogenic cell death than conventional dose rate irradiation with a dose enhancement factor at 10% survival (DEF10) of 1.310 and 1.365 for KPC and Panc02 cell lines, respectively. Ultra-high dose rate was equally potent in depleting CD3, CD4, CD8, and CD19 lymphocyte populations in both cardiac and splenic irradiation models of lymphopenia. Radiation-induced gastrointestinal toxicity was more pronounced and mouse survival (7 days vs. 15 days, p = 0.0001) was inferior in the ultra-high dose rate arm compared to conventional dose rate arm. These results suggest that, contrary to published data in other models of radiation-induced acute and chronic toxicity, dose rates of 35Gy/s do not protect mice from the detrimental side effects of irradiation in our models of cardiac and splenic radiation-induced lymphopenia or gastrointestinal mucosal injury.
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