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This work aimed at measuring cell-killing effectiveness of monoenergetic and Spread-Out Bragg Peak (SOBP) carbon-ion beams in normal and tumour cells with different radiation sensitivity. Clonogenic survival was assayed in normal and tumour human cell lines exhibiting different radiosensitivity to X- or gamma-rays following exposure to monoenergetic carbon-ion beams (incident LET 13-303 keV/microm) and at various positions along the ionization curve of a therapeutic carbon-ion beam, corresponding to three dose-averaged LET (LET(d)) values (40, 50 and 75 keV/microm). Chinese hamster V79 cells were also used. Carbon-ion effectiveness for cell inactivation generally increased with LET for monoenergetic beams, with the largest gain in cell-killing obtained in the cells most radioresistant to X- or gamma-rays. Such an increased effectiveness in cells less responsive to low LET radiation was found also for SOBP irradiation, but the latter was less effective compared with monoenergetic ion beams of the same LET. Our data show the superior effectiveness for cell-killing exhibited by carbon-ion beams compared to lower LET radiation, particularly in tumour cells radioresistant to X- or gamma-rays, hence the advantage of using such beams in radiotherapy. The observed lower effectiveness of SOBP irradiation compared to monoenergetic carbon beam irradiation argues against the radiobiological equivalence between dose-averaged LET in a point in the SOBP and the corresponding monoenergetic beams.

We measured residual cytogenetic damage in the progeny of human peripheral blood lymphocytes exposed to 1 GeV/ nucleon iron ions or gamma rays. Arm-specific DNA probes for chromosome 1 were used to detect aberrations as a function of dose in cells harvested 144 h after exposure. In addition, arm-specific mFISH was applied to samples exposed to a single dose of 2 Gy. These methods allowed the detection of interarm intrachanges (pericentric inversions) in addition to interchanges. The ratio of these types of aberrations (F ratio) has been proposed as a fingerprint of exposure to densely ionizing radiation. The fractions of aberrant cells in the progeny of cells exposed to iron ions were similar to those in the population exposed to gamma rays, possibly because many rearrangements induced by heavy ions ultimately lead to cell death. Simple inter- and intrachanges were also similar, but more complex rearrangements were found in cells that survived after exposure to iron ions. We did not find a significant difference in the ratio of simple interchanges to simple intrachanges for the two radiation types. However, iron ions induced a much higher frequency of events involving both inter- and intrachanges. We conclude that these complex rearrangements represent a hallmark of exposure to heavy ions and may be responsible of the decrease of the F ratio with increasing LET reported in the literature in some in vitro and in vivo experiments.

We report results for chromosomal aberrations in human peripheral blood lymphocytes after they were exposed to high-energy iron ions with or without shielding at the HIMAC, AGS and NSRL accelerators. Isolated lymphocytes were exposed to iron ions with energies between 200 and 5000 MeV/nucleon in the 0.1-1-Gy dose range. Shielding materials consisted of polyethylene, lucite (PMMA), carbon, aluminum and lead, with mass thickness ranging from 2 to 30 g/cm2. After exposure, lymphocytes were stimulated to grow in vitro, and chromosomes were prematurely condensed using a phosphatase inhibitor (calyculin A). Aberrations were scored using FISH painting. The yield of total interchromosomal exchanges (including dicentrics, translocations and complex rearrangements) increased linearly with dose or fluence in the range studied. Shielding decreased the effectiveness per unit dose of iron ions. The highest RBE value was measured with the 1 GeV/nucleon iron-ion beam at NSRL. However, the RBE for the induction of aberrations apparently is not well correlated with the mean LET. When shielding thickness was increased, the frequency of aberrations per particle incident on the shield increased for the 500 MeV/nucleon ions and decreased for the 1 GeV/nucleon ions. Maximum variation at equal mass thickness was obtained with light materials (polyethylene, carbon or PMMA). Variations in the yield of chromosomal aberrations per iron particle incident on the shield follow variations in the dose per incident particle behind the shield but can be modified by the different RBE of the mixed radiation field produced by nuclear fragmentation. The results suggest that shielding design models should be benchmarked using both physics and biological data.

We measured fluence and fragmentation of high-energy (1 or 5 A GeV) 56Fe ions accelerated at the Alternating Gradient Synchrotron or at the NASA Space Radiation Laboratory (Brookhaven National Laboratory, NY, USA) using solid-state CR-39 nuclear track detectors. Different targets (polyethylene, PMMA, C, Al, Pb) were used to produce a large spectrum of charged fragments. CR-39 plastics were exposed both in front and behind the shielding block (thickness ranging from 5 to 30 g/cm2) at a normal incidence and low fluence. The radiation dose deposited by surviving Fe ions and charged fragments was measured behind the shield using an ionization chamber. The distribution of the measured track size was exploited to distinguish the primary 56Fe ions tracks from the lighter fragments. Measurements of projectile's fluence in front of the shield were used to determine the dose per incident particle behind the block. Simultaneous measurements of primary 56Fe ion tracks in front and behind the shield were used to evaluate the fraction of surviving iron projectiles and the total charge-changing fragmentation cross-section. These physical measurements will be used to characterize the beam used in parallel biological experiments., (c2005 COSPAR. Published by Elsevier Ltd. All rights reserved.)

Abstract: The objective of this study was to measure differences in the chromosomal rearrangements found in the progeny of cells exposed to the same dose of X-rays or energetic iron ions, with emphasis on intra-chromosomal exchanges. We hybridized metaphase cells with human DNA probes specific for the p and q arms of the chromosome 1. The arm-specific probes allow a fast and reliable detection of both symmetrical and asymmetrical inter-chromosomal exchanges and inter-arm intra-changes (pericentric inversions) in the painted chromosome pair. We used this method to score aberrations in human peripheral blood lymphocytes exposed to 1Gy of either 250kVp X-rays or 1GeV/n Fe-ions and harvested following 120h in culture, including 2h in colcemid for metaphase-block. Although iron ions are much more effective than X-rays in the induction of chromosomal aberrations formed during the first post-exposure cell cycle, we found that the effectiveness drops when daughter cells are scored at a late harvest time. In fact, no significant difference in the yield of simple interchanges or intra-changes was found for the two radiation qualities. On the other hand, complex-type exchanges, including rearrangements involving both intra- and inter-chromosomal exchanges, were much more frequent in the progeny of the population exposed to Fe-nuclei than to photons. [Copyright &y& Elsevier]

Abstract: An automated analysis system was developed that is able to scan nuclear track detectors CR-39. The system consists of an optical microscope, a CCD camera, a frame grabber and a personal computer. On the latter a software written in Labview language (version 7.1) is implemented to control the motion of the microscope stage, the autofocus function and to measure the geometric characteristics of particle tracks. The system is able to detect and measure couples of partially overlapped tracks. As a preliminary application of this system, we estimated the projectile total charge-changing cross section for a 1GeV/n iron ion beam impacting a polyethylene target. [Copyright &y& Elsevier]

Abstract: Shielding is the only countermeasure currently available for exposure to cosmic radiation during space travel. We compared aluminum (Al) and polymethylmethacrylate (PMMA, or lucite) shields of 20g/cm2 thickness using 1GeV protons accelerated at the NASA Space Radiation Laboratory. The dose rate increased after the shield, and the increase was more pronounced after the Al than the PMMA shield. No significant differences in the induction of chromosomal aberrations were observed in human lymphocytes exposed to the same dose with no shield or behind the Al and PMMA blocks. However, the biological effectiveness per incident proton was increased by the shields. Simulations using the General-Purpose Particle and Heavy-Ion Transport Code System (PHITS) show that the increase in dose is caused by target fragments, and aluminum produces more secondary protons than PMMA. Nevertheless, the spectrum of particles behind the shield is confined within the low-LET region, and the biological effectiveness is consequently similar. [Copyright &y& Elsevier]