Quantification of damage to plasmid DNA from 35 MeV electrons, 228 MeV protons and 300 kVp X-rays in varying hydroxyl radical scavenging environments

Author:

Wanstall Hannah C1234,Henthorn Nicholas T356,Jones James47,Santina Elham56,Chadwick Amy L56,Angal-Kalinin Deepa47,Morris Geoffrey47,Warmenhoven John-William38,Smith Rob47,Mathisen Storm47,Merchant Michael J356,Jones Roger M124

Affiliation:

1. Department of Physics and Astronomy , Faculty of Science and Engineering, , Oxford Road, Manchester M13 9PL , UK

2. The University of Manchester , Faculty of Science and Engineering, , Oxford Road, Manchester M13 9PL , UK

3. Manchester Academic Health Science Centre, The Christie NHS Foundation Trust , Wilmslow Road, Manchester M20 4BX , UK

4. The Cockcroft Institute, Daresbury Laboratory , Daresbury, Warrington WA4 4AD , UK

5. Division of Cancer Sciences , Faculty of Biology, Medicine and Health, , Oxford Road, Manchester M13 9PL , UK

6. School of Medical Sciences, The University of Manchester , Faculty of Biology, Medicine and Health, , Oxford Road, Manchester M13 9PL , UK

7. ASTeC, STFC Daresbury Laboratory , Daresbury, Warrington WA4 4AD , UK

8. Division of Cancer Sciences, Faculty of Biology, Medicine and Health, School of Medical Sciences, The University of Manchester , Oxford Road, Manchester M13 9PL , UK

Abstract

Abstract The pBR322 plasmid DNA was irradiated with 35 MeV electrons, 228 MeV protons and 300 kVp X-rays to quantify DNA damage and make comparisons of DNA damage between radiation modalities. Plasmid was irradiated in a medium containing hydroxyl radical scavengers in varying concentrations. This altered the amount of indirect hydroxyl-mediated DNA damage, to create an environment that is more closely associated with a biological cell. We show that increasing hydroxyl scavenger concentration significantly reduced post-irradiation DNA damage to pBR322 plasmid DNA consistently and equally with three radiation modalities. At low scavenging capacities, irradiation with both 35 MeV electrons and 228 MeV protons resulted in increased DNA damage per dose compared with 300 kVp X-rays. We quantify both single-strand break (SSB) and double-strand break (DSB) induction between the modalities as a ratio of yields relative to X-rays, referred to as relative biological effectiveness (RBE). RBESSB values of 1.16 ± 0.15 and 1.18 ± 0.08 were calculated for protons and electrons, respectively, in a low hydroxyl scavenging environment containing 1 mM Tris–HCl for SSB induction. In higher hydroxyl scavenging capacity environments (above 1.1 × 106 s−1), no significant differences in DNA damage induction were found between radiation modalities when using SSB induction as a measure of RBE. Considering DSB induction, significant differences were only found between X-rays and 35 MeV electrons, with an RBEDSB of 1.72 ± 0.91 for 35 MeV electrons, indicating that electrons result in significantly more SSBs and DSBs per unit of dose than 300 kVp X-rays.

Funder

UK Research and Innovation

Engineering and Physical Sciences Research Council

Science and Technology Facilities Council

Cockcroft Institute

Publisher

Oxford University Press (OUP)

Subject

Health, Toxicology and Mutagenesis,Radiology, Nuclear Medicine and imaging,Radiation

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