Biological Effectiveness of Accelerated Protons for Chromosome Exchanges.

Kerry A. George,Francis A. Cucinotta,Megumi Hada

doi:10.3389/fonc.2015.00226

Kerry A. George, Francis A. Cucinotta + Show 1 more

Open Access

https://doi.org/10.3389/fonc.2015.00226

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Abstract

We have investigated chromosome exchanges induced in human cells by seven different energies of protons (5–2500 MeV) with LET values ranging from 0.2 to 8 keV/μm. Human lymphocytes were irradiated in vitro and chromosome damage was assessed using three-color fluorescence in situ hybridization chromosome painting in chemically condensed chromosomes collected during the first cell division post irradiation. The relative biological effectiveness (RBE) was calculated from the initial slope of the dose–response curve for chromosome exchanges with respect to low dose and low dose-rate γ-rays (denoted as RBEmax), and relative to acute doses of γ-rays (denoted as RBEγAcute). The linear dose–response term was similar for all energies of protons, suggesting that the decrease in LET with increasing proton energy was balanced by the increase in dose from the production of nuclear secondaries. Secondary particles increase slowly above energies of a few hundred megaelectronvolts. Additional studies of 50 g/cm2 aluminum shielded high-energy proton beams showed minor differences compared to the unshielded protons and lower RBE values found for shielded in comparison to unshielded beams of 2 or 2.5 GeV. All energies of protons produced a much higher percentage of complex-type chromosome exchanges when compared to acute doses of γ-rays. The implications of these results for space radiation protection and proton therapy are discussed.

Highlights

The study of the biological effectiveness of accelerated proton exposures is of interest for clinical treatment plans and for assessing normal tissue damage from protons of various energies that are generated outside of the Bragg peak during proton therapy [1,2,3,4]
Evidence indicates that relative biological effectiveness (RBE) varies considerably along the proton depthdose distribution, RBE modeling in treatment planning still involves significant uncertainties and, clinical proton therapy is usually based on the use of a generic RBE of 1.1 [4]
Whole blood was collected from healthy volunteers and was irradiated with accelerated protons using the NASA Space Radiation Laboratory (NSRL) facility at Brookhaven National Laboratory (BNL)

Summary

Introduction

The study of the biological effectiveness of accelerated proton exposures is of interest for clinical treatment plans and for assessing normal tissue damage from protons of various energies that are generated outside of the Bragg peak during proton therapy [1,2,3,4]. Evidence indicates that relative biological effectiveness (RBE) varies considerably along the proton depthdose distribution, RBE modeling in treatment planning still involves significant uncertainties and, clinical proton therapy is usually based on the use of a generic RBE of 1.1 [4]. Experimental studies have shown that the RBE of protons varies with biological endpoint, tissue type, dose, and energy of the protons. High-energy protons induce nuclear spallation and other interactions that produce secondary protons, neutrons, and heavy ion fragments. Nuclear interaction cross sections generally increase with the energy of the protons [3], and the secondary particles typically have higher LET values that can increase RBE

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