Cellular Response to Proton Irradiation: A Simulation Study with TOPAS-nBio
- Massachusetts General Hospital, Boston, MA (United States); Tsinghua Univ., Beijing (China); Tsinghua Univ., Beijing (China). Key Lab. of Particle & Radiation Imaging
- Massachusetts General Hospital, Boston, MA (United States); Harvard Medical School, Boston, MA (United States)
- Queens Univ., Belfast (United Kingdom). Center for Cancer Research and Cell Biology
- Univ. of California, San Francisco, CA (United States)
- Univ. of Manchester (United Kingdom)
- SLAC National Accelerator Lab., Menlo Park, CA (United States)
- Tsinghua Univ., Beijing (China); Tsinghua Univ., Beijing (China). Key Lab. of Particle & Radiation Imaging
The cellular response to ionizing radiation continues to be of significant research interest in cancer radiotherapy, and DNA is recognized as the critical target for most of the biologic effects of radiation. Incident particles can cause initial DNA damages through physical and chemical interactions within a short time scale. Initial DNA damages can undergo repair via different pathways available at different stages of the cell cycle. The misrepair of DNA damage results in genomic rearrangement and causes mutations and chromosome aberrations, which are drivers of cell death. This work presents an integrated study of simulating cell response after proton irradiation with energies of 0.5–500 MeV (LET of 60–0.2 keV/µm). A model of a whole nucleus with fractal DNA geometry was implemented in TOPAS-nBio for initial DNA damage simulations. The default physics and chemistry models in TOPAS-nBio were used to describe interactions of primary particles, secondary particles, and radiolysis products within the nucleus. The initial DNA double-strand break (DSB) yield was found to increase from 6.5 DSB/Gy/Gbp at low-linear energy transfer (LET) of 0.2 keV/µm to 21.2 DSB/Gy/Gbp at high LET of 60 keV/µm. A mechanistic repair model was applied to predict the characteristics of DNA damage repair and dose response of chromosome aberrations. It was found that more than 95% of the DSBs are repaired within the first 24 h and the misrepaired DSB fraction increases rapidly with LET and reaches 15.8% at 60 keV/µm with an estimated chromosome aberration detection threshold of 3 Mbp. The dicentric and acentric fragment yields and the dose response of micronuclei formation after proton irradiation were calculated and compared with experimental results.
- Research Organization:
- SLAC National Accelerator Laboratory (SLAC), Menlo Park, CA (United States)
- Sponsoring Organization:
- USDOE Office of Science (SC), Basic Energy Sciences (BES); Horizon 2020; National Cancer Institute
- Grant/Contract Number:
- AC02-76SF00515
- OSTI ID:
- 1647027
- Journal Information:
- Radiation Research, Journal Name: Radiation Research Journal Issue: 1 Vol. 194; ISSN 0033-7587
- Publisher:
- Radiation Research SocietyCopyright Statement
- Country of Publication:
- United States
- Language:
- English
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