SPACE RADIATION SHIELDING: BIOLOGICAL EFFECTS OF ACCELERATED IRON IONS AND THEIR MODIFICATION BY ALUMINUM OR LUCITE SHIELDS

M. Durante1*, F. Antonelli2, F. Ballarini3, M. Belli2, D. Bettega3, M. Biaggi3, P. Calzolari3, A. Ferrari4, G. Gialanella1, A. Giussani3, G. Grossi1, P. Massariello3, A. Ottolenghi3, M. Pugliese1, P. Scampoli1, G. Simone2, E. Sorrentino2, M.A. Tabocchini2, L. Tallone3

1. Università "Federico II", Napoli, Italy; 2. Istituto Superiore di Sanità, Roma, Italy; 3. Università di Milano, Italy; 4. CERN, Geneva, Switzerland

ABSTRACT The research program described here is focused on the effect of the shielding on the biological effects of heavy ions. Both experiments and models are included in the program. Experiments aim to determine genetic effects of heavy ions with or without shielding. Mathematical models, based on Monte Carlo codes, will be used to interpret the biological results. The final goal is to get a feasible model able to predict the radiation-induced biological damage in space, given the free- space radiation field and the spacecraft shielding. Preliminary results about chromosomal aberrations in human peripheral blood lymphocytes induced by accelerated 56Fe ions are presented here.

INTRODUCTION

For terrestrial radiation workers, protection against radiation exposure can be provided through shielding of the radiation source. In extra-terrestrial space, shielding is effective against trapped protons, but its efficiency is poor against galactic cosmic rays (GCR) penetration. Indeed, high-energy particle radiation in space is very penetrating and GCR produce a large number of secondary particles, including neutrons, generated by nuclear interactions with the nuclei in the shield. These particles have generally lower energy, but can have higher quality factors than incident primary cosmic particles [1]. Considering the current uncertainties in space radiation physics and biology, NASA [2] has pointed out that major improvements are urgently needed in a) models of biological response in monochromatic and mixed charged particle fields, and b) experiments on biological effects of heavy ions with shielding. For this very reason, we have established a large International collaboration to measure the biological effects of heavy ions and their modification by shielding [3]. The goal of the project is to gather experimental data on the RBE of accelerated heavy ions for genetic effects in human cells, namely DNA double-strand breaks, chromosomal aberrations, and lethal mutations. These data will be used to improve and validate Monte Carlo computer models of shield performance. In this paper, we present preliminary results obtained at the HIMAC accelerator (Chiba, Japan) with 56Fe-ions.

MATERIALS AND METHODS

Accelerated 56Fe beams were obtained at the HIMAC accelerator in Chiba, Japan. Characteristics of the beams are described in Table 1. Monitoring and dosimetry of the heavy-ion beams at the HIMAC accelerator are described elsewhere [4]. We used two different shields: PMMA (lucite), a low-Z plastic material (= 1.16 g/cm3), and aluminium ( = 2.7 g/cm3), the usual spacecraft shield. Thickness of the two shields were chosen to reduce the residual range of the 500 MeV/n beam to the same value of the 200 MeV/n unattenuated iron beam.

* Author to whom correspondence should be addressed at: Dipartimento di Scienze Fisiche, Università "Federico II", Montre S. Angelo, Via Cintia, 80126 Napoli, Italy. E-mail: [email protected]

1 Biological samples were human peripheral blood lymphocytes obtained by a healthy donor and isolated by centrifugation in Ficoll gradients. Isolated lymphocytes were resuspended in RPMI1640 growth medium and exposed at room temperature at a dose rate around 1 Gy/min. Following exposure, samples were incubated at 37 °C in medium supplemented with 1% phytohemagglutinin. After 48 h, chromosomes were prematurely condensed by calyculin A (50 nM) for 1 h at 37 °C following the original protocol described by Durante et al. [5]. Slides were hybridized in situ with DNA fluorescent probes specific for human chromosomes 1 and 2. All kinds of chromosome aberrations were scored in prematurely condensed chromosomes 1 and 2, including translocations, dicentrics, excess fragments, and complex-type exchanges.

Energy in Energy on Shielding Residual range LET Fraction of 56 vacuum sample (mm) in H2O (keV/m) Fe ions in the (MeV/n) (MeV/n) beam at sample position 500 414 - 71.6 184.9 1 500 PMMA (56 mm) 8 0.40 500 Al (30 mm) 8 0.46 200 114 - 8.03 302.2 1 Table 1. Characteristics of the 56Fe beams used at the HIMAC accelerator in Chiba (Japan).

RESULTS AND DISCUSSION

The fraction of aberrant lymphocytes (i.e., the fraction of scored cells displaying any type of visible structural aberration involving painted chromosomes 1 and/or 2) is plotted vs. the radiation dose at the sample position in Figure 1. It can be noted that iron beams are more efficient than X- rays in the induction of chromosomal aberrations, and the 500 MeV/n beam is more efficient then the 200 MeV/n beam. As a function of dose at the sample position, no significant differences are

Figure 1. Dose-response curve for the Figure 2. Fluence-response curve for induction of chromosomal aberrations in the induction of chromosomal human lymphocytes exposed to X-rays or aberrations in human lymphocytes 56Fe accelerated beams. Y-axis: fraction of exposed to 56Fe accelerated beams. Y- lymphocytes with aberrations in prematurely axis: fraction of lymphocytes with condensed chromosomes 1 or 2. X-axis: aberrations in prematurely condensed dose measured in the sample position. chromosomes 1 or 2. X-axis: fluence of iron ions incident on the shielding.

2 observed for the 500 MeV/n beams unshielded or shielded with Al or PMMA. The same data are plotted in Figure 2 as a function of the 56Fe ions fluence incident on the shield. The 500 MeV/n ions induce chromosomal aberrations more efficiently than the 200 MeV/n ions. The shield increases the effectiveness per ion of the 500 MeV/n beam, and the cytogenetic damage behind the 56 mm lucite shield seems to be slightly higher than behind a 30 mm Al shield. Data in Figure 1 basically show that the radiation spectrum produced by the shield does not significantly change the quality factor. In fact, cytogenetic damage is similar at the same radiation dose absorbed by the sample. However, when plotted as a function of the number of ions hitting the shield, the curves are separated and the shield increases the effectiveness per unit ion. The difference is caused by nuclear fragmentation of the beam in the target. A lower number of Fe ions are required to produce a certain dose at the sample when the sample is shielded either with Al or PMMA. Wilson et al. [6] showed that the shield performance is dependent upon shield material and thickness, as well as incident beam energy and charge. Their calculations suggest that the biological effectiveness of GCR can be increased behind thin shields made by high atomic number materials. Results in Figure 2 give the first experimental evidence of this possible deleterious effect of space radiation shielding. Preliminary data obtained at the HIMAC accelerator and at the AGS accelerator in Brookhaven, Upton (USA) on human cellular DNA fragmentation induced by 56Fe beams of various energies, without and with shielding, support this hypothesis.

ACKNOWLEDGEMENTS

This research project is generously supported by the Italian Space Agency (ASI), and involves Italian radiation biophysics groups (Universities of Milan and Naples, National Institute of Health in Rome), in collaboration with NASA (USA), NIRS (Japan), CERN (Switzerland), Brookhaven National Laboratories (USA), and TERA (Italy).

REFERENCES

1. F.A. Cucinotta and J.W. Wilson, Assessment of current shielding issues. In: Shielding Strategies for Human Space Exploration (J.W. Wilson, J. Miller, A. Konradi, and F.A. Cucinotta, editors), NASA-CP 3360, 1997, pp. 447-467. 2. NASA, Life Sciences Division. Strategic Program Plan for Space Radiation Health Research. NASA, Washington DC, 1999. 3. M. Durante, Influence of the shielding on the space radiation biological effectiveness. Physica Medica 17 (suppl. 1): 2001, 269-271. 4. T. Kanai, M. Endo, S. Minohara, N. Miyahara, H. Koyama-ito, H. Tomura, N. Matsufuji, Y. Futami, A. Fukumura, T. Hiraoka, Y. Furusawa, K. Ando, M. Suzuki, F. Soga and K.Kawachi, Biophysical characteristics of HIMAC clinical irradiation system for heavy-ion radiation therapy. Int. J Radiat. Oncol. Biol. Phys. 44: 1999, 201-210. 5. M. Durante, Y. Furusawa and E. Gotoh, A simple method for simultaneous interphase- metaphase chromosome analysis in biological dosimetry. Int. J. Radiat. Biol. 74: 1998, 457-462. 6. J.W. Wilson, F.A. Cucinotta, M.-H. Kim and W. Schimmerling, Optimized shielding for space radiation protection. Physica Medica 17 (suppl. 1): 2001, 67-71.

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