Master Thesis

DKFZ-2022-02712

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png The FLASH Effect In Vitro - MechanisticInvestigations With Ultra-High Dose Rate X-RaysIn Hypoxia And Normoxia

Knoll, J.DKFZ*

2022

Abstract: Recently, the discovery that irradiation at ultra-high in comparison to conventionallyapplied dose rates can benefit healthy tissue while preserving the same level of tumourcontrol has attracted a lot of attention in radiobiological research. However, despite severalhypotheses to explain the underlying mechanism, there is so far no conclusive answer asto what causes the ’FLASH effect’.The present thesis employed experiments with human tumour cells irradiated withX-rays to investigate the connection between FLASH sparing and the surrounding oxygenconcentration. In a second set of experiments, a potential enzymatic FLASH mechanismwas examined by targeting the cytoplasmic antioxidant enzyme SOD1.In line with published in vitro data, it was found that FLASH sparing increases bothwith dose rate and increasing oxygen concentration thereby dismissing radiolytical oxygendepletion as a potential mechanism. Surprisingly, the observed effect was also present atdose rates commonly considered too low for FLASH research. The results also rule out akey role of SOD1 in the FLASH mechanism and instead point to other antioxidants likethe mitochondrial SOD2.In summay, this thesis underlines the importance of oxygen and the cellular antoxidantsystem for the FLASH effect and demonstrates the applicability of cell culture research inthis context.

Note: Masterarbeit, Universität Heidelberg, 2022

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Contributing Institute(s):

1. E041 Med. Physik in der Radioonkologie (E041)

Research Program(s):

1. 315 - Bildgebung und Radioonkologie (POF4-315) (POF4-315)

Appears in the scientific report 2022

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