[Triumf-seminars] TRIUMF Special Seminar, Tue 2022-03-29 at 14:00

[TRIUMF Seminars]

Date/Time: Tue 2022-03-29 at 14:00  

Location: Auditorium + Remote  

Speaker: Dayna Latney (San Diego State U)  

Title: Quantifying DNA Damaging Effects of FLASH Irradiation - A Plasmid DNA Study  

Abstract: FLASH radiotherapy is a newly developing technique that could significantly improve the effectiveness of clinical radiotherapy. Pre-clinical studies have shown that irradiation at FLASH dose rates (>40 Gy/s) significantly reduces normal tissue toxicities while achieving tumor control comparable to conventional dose rates (~0.1 Gy/s). However, the mechanisms explaining this effect remain unclear. Our study aims to compare the DNA damaging effects of FLASH versus conventional dose rate photon irradiation on plasmid DNA. We constructed transportable square polycarbonate phantoms with an 8.5 mm^3 central cylindrical cavity. Plasmid DNA (>95% supercoiled pBR322) was pipetted into each phantom and sealed inside with an aluminum induction seal followed by a vacuum seal. These samples will be irradiated to 10, 20, and 30 Gy in duplicate using a 10 MV FLASH and conventional photon beam, 100 and 0.1 Gy/s, respectively. The FLASH beam will be delivered using a modified linac at TRIUMF
  and the conventional beam using a clinical linac at Genesis Healthcare Partners in San Diego. Plasmid DNA has three naturally occurring conformations (supercoiled, open-circular, and linear corresponding to undamaged DNA, single strand break (SSB), and double strand break (DSB), respectively). After irradiation, agarose gel electrophoresis will be used to separate and quantify corresponding relative intensities to calculate percent yields of each conformation. The calculated percent yields will be used to model DNA strand break damage as a function of dose. This procedure will be repeated for samples to receive a post-irradiation treatment with base excision repair enzymes, Fpg (formamidopyrimidine [fapy]-DNA glycosylase) and Endonuclease III (Nth), to quantify irradiation induced isolated and clustered oxidized DNA base damage. 

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