George D. Jones (United Kingdom)

University of Leicester Leicester Cancer Research Centre
My research may be summarised as: ‘Mechanisms, Measurement and Consequences of Radiation-Induced Damage to DNA’ to enhance the benefits of the radiotherapy treatment of cancer. Emphasis is placed on studying clinically relevant doses (avoiding the uncertainty of extrapolation from higher doses) and bio-relevant models, and on translational research themes with anticipated patient benefit - such as FLASH!!

Author Of 1 Presentation

 Conference Calendar

COMET ASSAY MEASURES INDICATE LOWER DNA DAMAGE LEVELS IN WHOLE BLOOD PBLS FOLLOWING EX VIVO ELECTRON FLASH EXPOSURES OVER 0.25-1% OXYGEN.

Session Name
0660 - Biology II (ID 25)
Session Type
FLASH Mechanisms Track (Oral Presentations)
Date
Fri, 03.12.2021
Session Time
10:50 - 11:50
Room
Room 2.15
Presenter
Lecture Time
10:50 - 11:00

Abstract

Background and Aims

In vivo studies report the normal tissue sparing effects of FLASH radiotherapy compared to conventional dose rate therapy (CONV). Towards this, it is proposed that FLASH causes a transient/local hypoxia so reducing the level of induced DNA damage for FLASH vs. CONV exposure. Therefore, aim of this study is to assess the levels of DNA damage in whole blood PBLs induced by FLASH vs. CONV irradiation under different oxygen concentrations ex vivo.

Methods

Samples of whole blood were irradiated at different oxygen concentrations (ranging between 0.25 and 21%) with a 6 MeV electron beam at a dose rate of either 2 kGy/s (FLASH) or 0.1 Gy/s (CONV). Induced DNA damage levels in whole blood PBLs were evaluated by alkaline Comet assay after 20 Gy irradiation.

Results

<10% difference was noted between the DNA damage levels induced following FLASH and CONV irradiation under normoxic conditions (21% O2). However, following irradiation over 0.25-1% oxygen, lower levels of DNA damage were clearly induced following FLASH exposure, the difference being significant at 0.5% O2. Furthermore, dose-response studies show the FLASH effect to be lost at ≤10Gy.

Conclusions

This study extends our earlier preliminary findings and substantiates that lower levels of DNA damage are induced following FLASH exposure under low oxygen tension, supporting transient radiation-induced hypoxia/ transient oxygen depletion as a mechanism possibly contributing to the tissue sparing effect of FLASH radiotherapy. Further studies to characterise the induced-damage manifest by FLASH and to dissect/differentiate the exact mechanisms involved (radical-radical recombination vs. transient oxygen depletion) will be presented/discussed.

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Presenter of 1 Presentation

 Conference Calendar

COMET ASSAY MEASURES INDICATE LOWER DNA DAMAGE LEVELS IN WHOLE BLOOD PBLS FOLLOWING EX VIVO ELECTRON FLASH EXPOSURES OVER 0.25-1% OXYGEN.

Session Name
0660 - Biology II (ID 25)
Session Type
FLASH Mechanisms Track (Oral Presentations)
Date
Fri, 03.12.2021
Session Time
10:50 - 11:50
Room
Room 2.15
Presenter
Lecture Time
10:50 - 11:00

Abstract

Background and Aims

In vivo studies report the normal tissue sparing effects of FLASH radiotherapy compared to conventional dose rate therapy (CONV). Towards this, it is proposed that FLASH causes a transient/local hypoxia so reducing the level of induced DNA damage for FLASH vs. CONV exposure. Therefore, aim of this study is to assess the levels of DNA damage in whole blood PBLs induced by FLASH vs. CONV irradiation under different oxygen concentrations ex vivo.

Methods

Samples of whole blood were irradiated at different oxygen concentrations (ranging between 0.25 and 21%) with a 6 MeV electron beam at a dose rate of either 2 kGy/s (FLASH) or 0.1 Gy/s (CONV). Induced DNA damage levels in whole blood PBLs were evaluated by alkaline Comet assay after 20 Gy irradiation.

Results

<10% difference was noted between the DNA damage levels induced following FLASH and CONV irradiation under normoxic conditions (21% O2). However, following irradiation over 0.25-1% oxygen, lower levels of DNA damage were clearly induced following FLASH exposure, the difference being significant at 0.5% O2. Furthermore, dose-response studies show the FLASH effect to be lost at ≤10Gy.

Conclusions

This study extends our earlier preliminary findings and substantiates that lower levels of DNA damage are induced following FLASH exposure under low oxygen tension, supporting transient radiation-induced hypoxia/ transient oxygen depletion as a mechanism possibly contributing to the tissue sparing effect of FLASH radiotherapy. Further studies to characterise the induced-damage manifest by FLASH and to dissect/differentiate the exact mechanisms involved (radical-radical recombination vs. transient oxygen depletion) will be presented/discussed.

Hide