Direct Measurement of DNA Damage to Determine Dose and Biological Effectiveness 📝

Author: Michael Lamontagne, Ileana Pazos, Jerimy C. Polf, Joseph W. Robertson, Teniola Tobun, Ronald E. Tosh, Michael Zwolak 👨‍🔬

Affiliation: Biophysics and Biomedical Research Group, Microsystems and Nanotechnology Division, National Institute of Standards and Technology, M3D, Inc, National Institute of Standards and Technology, Dosimetry Group, Radiation Physics Division, National Institute of Standards and Technology 🌍

Abstract:

Purpose: To study how damage to DNA molecules increases and changes as a function of the type and dose of radiation.

Methods: DNA molecules of a known length (number of base pairs (BP)) within a new nanopipette detector were irradiated with 60CO gammas and a 150 MeV clinical proton beam at depths (increasing LET) of 0 cm, 0.5 cm, 7.5 cm, and 15 cm (at the Bragg peak) within a tissue equivalent plastic phantom with doses ranging from 1 Gy to 20 Gy. Changes to the length of the DNA were measured with a shortening of the DNA length indicating a double strand break (DSB) had occurred in the molecule during irradiation. DNA damage (DSBs) was studied as a function of dose delivered. Differences in the DNA damage caused by 60Co gammas and protons at different phantom depths were qualitatively studied as potential causes for changes in proton relative biological effectiveness along the depth of the proton Bragg peak.

Results: As the dose increased the DNA damage (DSBs) increased, as seen by the reduction of full initial length DNA molecules in the irradiated samples. The percent of damaged DNA molecules increased linearly with delivered dose up to ~7 Gy, with DNA damage increasing supra-linearly for higher doses. Additionally, protons were seen to cause more DNA damage (more DSBs) per Gy than gammas, and the percent of damaged DNA per dose changed as the depth (LET) in the phantom increased up to the depth of the Bragg peak.

Conclusion: Reduction in DNA length, and thus DSBs, were directly measured with the new nanopipette detectors. Our studies indicate DSB induction in DNA is linear with the gamma and proton dose delivered for doses under 7 Gy, and that protons were more efficient at inducing DSBs than gammas per Gy of dose.

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