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Investigation of the Spatial Ionization Density Dependence of the DNA Damage in a Lung Cancer Cell Line with Proton Irradiations

F Guan

F Guan*, L Bronk , M Kerr , D Ma , Y Wang , X Wang , Y Li , O Vassiliev , D Patel , U Titt , S Lin , D Grosshans , R Mohan , UT MD Anderson Cancer Center, Houston, TX


TH-AB-605-8 (Thursday, August 3, 2017) 7:30 AM - 9:30 AM Room: 605

Purpose: To investigate the relationship between DNA damage in cancer cells and the spatial ionization density from a mono-energetic proton beam using the inmmunofluorescent foci staining technique and track-structure Monte Carlo simulations.

Methods: We have designed a versatile irradiation system to investigate the biological effects of protons with different physical parameters along a pristine Bragg curve. We used 96-well plates to culture cells where the eight wells in each column received the same physical parameters. We used the track-structure Monte Carlo package Geant4-DNA to model the detailed interactions (ionization and excitations, etc.) of particles with cell layers (5 µm water). We used an 81.4 MeV scanning proton beam to irradiate H460 lung cancer cells. After the irradiation, we examined the DNA double-strand break (DSB) time-dependent repair kinetics by quantifying the established DSB marker 53BP1.

Results: Monte Carlo calculation results showed that the total energy depositions are mainly from ionizations. The cell irradiation results were normalized to obtain the average number of foci per nucleus per ionization at different time points post-irradiation for each column in the 96-well plates. For column #1 in the entrance area of a Bragg curve, the spatial ionization density is 42.0 per incident proton per micron, and the average number of foci per nucleus per ionization is 1.58×10⁻¹² ± 1.23 × 10⁻¹³ at 24 hours post irradiation. For column #7 at Bragg peak, the corresponding values are 335.7 and 4.58×10⁻¹² ± 1.23× 10⁻¹³. For column #12 in the distal edge of a Bragg curve, the values are 543.4 and 1.31×10⁻¹¹ ± 3.55× 10⁻¹³.

Conclusion: Our results show that the DNA damage following proton irradiation has a strong dependence on the spatial ionization density and increases in a non-linear trend. This observation supports our previously published data showing a non-linear relationship between proton RBE and LET.

Funding Support, Disclosures, and Conflict of Interest: This research is supported by 2016 AAPM Research Seed Funding Grant.

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