Radiation Protection Dosimetry Advance Access published May 12, 2015 Radiation Protection Dosimetry (2015), pp. 1–4

doi:10.1093/rpd/ncv301

NANODOSIMETRY OF ELECTRONS: ANALYSIS BY EXPERIMENT AND MODELLING A. Bantsar and S. Pszona* National Centre for Nuclear Research, Otwock, Swierk 05-400, Poland *Corresponding author: [email protected]

INTRODUCTION Electrons as primary and secondary radiation are widely applied in many radiobiological experiments as well as for radiotherapy purposes. The energy spectra of electrons in these applications range from high-energy electrons as secondaries generated by X and gamma radiation through beta radiation emitters administered internally to low-energy primary electrons emitted by 125I for targeted radiotherapy. Soft X rays in the form of the CK line from carbon, Al and Ti (which in turn generates low-energy electrons due to the photoelectric effect in irradiated tissues) have been used for radiobiological studies. The energy of electrons applied for different purposes extends from 100 eV (high linear energy transfer, LET) to the MeV range (low LET). Both theoretical and experimental approaches have been employed to advance the understanding of how these electrons interact with nanosites. The spectrum of initial DNA damage created by electrons has been modelled by the Monte Carlo method by Nikjoo et al. (1) This work revealed the complexity of these damages. Besides the damage caused by single-strand breaks (SSB) and doublestrand breaks (DSB), additional strand breakages are also probable. Even low LET radiation (electrons) could yield a complex damage to DNA. Among the nanodosimetry methods developed recently(2 – 5) only the Jet Counter operated at National Centre for Nuclear Research is available for the experiments conducted with electrons. The nanodosimetric experimental data for low-energy electrons(6) specifically for Auger electrons of the 125I source(6) have been published. The present study is aimed at reporting the results of nanodosimetric experiments with highenergy electrons emitted by a 131I source. The nanodosimetry approach presented here is based on the analysis of the spectra derived from the formation of ionisation clusters at nanosites caused by single charged particles(7). As suggested in the earlier work

of Grosswendt et al.(8), the distribution of the sizes of ionisation clusters caused by a charged particle acting in nanometer-sized targets of various volumes could serve as the basic descriptors of radiation damage to DNA. These basic descriptors have been formulated and can be summarised as the measured quantity is a distribution of probability of exactly n cluster size, Pn(T,Dr) for a given energy T and nanosite diameter D. The plot of Pn(T,Dr) against n yields an ionisation cluster-size distribution, ICSD. The derived quantities from ICSD are: first moment M1 and cumulative distribution function Fk. The present study reports (1) the experimental results of ICSD from 131I source electrons interacting with nitrogen-simulated DNA sites. (2) a comparison of the experimental results with Monte Carlo modelling. (3) a comparison of the experimental results with the existing models (based on calculations) of complex damage to DNA. MATERIALS AND METHODS The experiments were carried out using the Jet Counter as described elsewhere(9).The quantity being measured is the ionisation cluster-size distribution, ICSD. The diameters of the simulated nitrogen sites (SNS) which are irradiated by a single electron emitted from a source had mass per area values ranging from 0.16 to 1.7 mg cm22. The overall efficiency of single ion counting has been previously investigated(10,11) and has been estimated as 0.47 within 5 % uncertainty (rounded here to 0.5). RESULTS Experiments with high-energy electrons A radioactive source of 131I emitting beta particles with maximum energy of 606 keV (with mean energy

# The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: [email protected]

Downloaded from http://rpd.oxfordjournals.org/ at North Dakota State University on May 19, 2015

Nanodosimetry experiments for high-energy electrons from a 131I radioactive source interacting with gaseous nitrogen with sizes on a scale equivalent to the mass per area of a segment of DNA and nucleosome are described. The discrete ionisation clustersize distributions were measured in experiments carried out with the Jet Counter. The experimental results were compared with those obtained by Monte Carlo modelling. The descriptors of radiation damages have been derived from the data obtained from ionisation cluster-size distributions.

A. BANTSAR AND S. PSZONA

volume). The measured quantity is a distribution of the probability of exactly n cluster size, Pn(T, Dr), for a given energy T and nanosite diameter Dr as a function of cluster size n. The plot of Pn(T,Dr) against n forms an ionisation cluster-size distribution, ICSD. The basic nanodosimetric descriptors of a charged particle are: the first moment M1(T,Dr) of an ICSD and the cumulative distribution Fk (T,Dr). These descriptors can be derived from measured ionisation cluster distribution spectra. The first moment, M1(T,Dr) of an ICSD for a given electron energy T and for a given nanosite Dr is defined as M1 ðTÞ ¼

1 X n¼0

nPn ðTÞ;

1 X

Pn ðQ; dÞ ¼ 1

ð1Þ

n¼0

Derivation of nanodosimetric descriptors from ionisation cluster-size spectra for electrons The basic stochastic quantity is the ionisation cluster size (ICS) is defined as exactly n number of ionisations which are produced by an ionising particle with energy T in a specified track segment (or target

Figure 1. The measured ionisation cluster-size distribution (ICSD) values for nitrogen cylinders of different diameters (Dr): 0.16 (squares), 0.32 (dots), 0.66 (triangles), 1.21 (diamonds) and 1.7 (reversed triangles) mg cm22. The geometry of irradiation is indicated in the diagram, upper right corner.

Figure 2. The Monte Carlo modelled ionisation cluster-size distributions for 100 % of ion collection and for nitrogen cylinders of different diameters (Dr). (Range of values given at upper right corner.)

Figure 3. The comparison of the measured ICSD values (closed symbols and solid lines) with the modelled values (open symbols and solid lines) for nitrogen cylinders of selected diameters (Dr).

Page 2 of 4

Downloaded from http://rpd.oxfordjournals.org/ at North Dakota State University on May 19, 2015

190 keV) was used as a source of high-energy electrons. The 131I source is produced by electrodeposition method on the head surface of a silver rod, 0.5 mm in diameter. The estimated source radioactivity at the beginning of the experiments was 120 kBq. This activity gives around Nmean ¼ 3 electrons per gas jet. This source was positioned at the entrance hole of the interaction chamber (IC) at half of its height. The geometry of irradiation of the nanosite nitrogen volume by electrons is illustrated in Figure 1. Each single electron emitted by the source enters the IC, interacts stochastically with the cylindrical gas nanosite and produces an ionisation cluster which is then registered in an event-by-event manner. The results of the measured cluster-size distribution generated by electrons emitted by the 131I source in different nanovolumes, corrected for the decay time and Nmean, are shown in Figure 1. These distributions were obtained for the extended range of nitrogen nanosites characterised by its diameter from 0.16 to 1.7 mg cm22. Parallel to these measurements, the experiment was also modelled by the Monte Carlo method for the same range of diameters of the nanosites and for 100 % efficiency of ion counting (Figure 2). A comparison of both measured and calculated ICSD values for selected nanosites showed qualitative agreement for the two methods (Figure 3).

NANODOSIMETRY OF ELECTRONS

Figure 5. The plot of the cumulative distribution function F2, measured ( points) and calculated (solid line) as a function of the reduced diameters (h Dr).

Figure 6. Cumulative distributions F2 as a function of sensitive diameter for 125I and 131I. Open symbols, modelling; full squares, experimental results.

function Fk for k  2. Grosswendt first noted the usefulness of this quantity(10) and showed that F2, i.e. Fk for k  2, is well correlated with the cross section for DSBs observed in SV 40 viral form DNA when irradiated by very different charged particles. The values for F2 for-131I and 125I electrons derived from modelling and the nanodosimetric experiments appear in Figure 6. The maximum of F2 occurs for 125I electrons while for 131I electrons are more than two orders of magnitude lower. The F2 function describes the ability to damage DNA with DSBs and more complex strand breaks. In the ionisation cluster-size distribution for 131I electrons (Figures 1 and 2), one can recognise that for a nanosite with the diameter 0.66 mg cm22 (which is equivalent to 2 nm of liquid water) many cluster sizes .2 can be observed. These means that one can expect corresponding complex damages to DNA despite low LET of these electrons. These results support Goodhead’s (11) statement that:

The cumulative distribution is given as Fk ðTÞ ¼

1 X

Pn ðTÞ

ð2Þ

n¼k

Figures 4 and 5 illustrates the first moment of the experimentally measured ICSD values together with the calculated values. The measured and calculated values for M1 showed reasonable agreement. DISCUSSION The nanodosimetric experiments with high-energy electrons presented here as well as the earlier results for low monoenergetic electrons(6) and the nanodosimetry of Auger electrons(12) have formed a basis for the conclusions about the ability of electrons to damage DNA. For this purpose, the nanodosimetry method uses the concept of a cumulative distribution

For all radiation a high proportion of the DSB are complex (i.e. they have at least one additional break); the proportion rises from 20 % for high energy electrons (typical low –LET radiations) to 30 % for very low –energy electrons (an abundant component of all low- LET radiations) and up to 70 % for high LET alpha particles. The measured cluster-size distribution for 131I electrons (and for nanosite nitrogen with diameter equal to 0.66 mg cm22) has been compared with the existing modelled data(1) with respect to the yields of the complex damages to DNA. Such comparison with the data from different approaches requires only one condition that both are related to the same basic medium, liquid water Therefore, the mechanistic comparison of both approaches seems to be acceptable. As it has been shown by Nikjoo(1), the low LET radiation yields a variety of types of strand breaks.

Page 3 of 4

Downloaded from http://rpd.oxfordjournals.org/ at North Dakota State University on May 19, 2015

Figure 4. The plots of the first moments, M1, measured and calculated as a function of ‘reduced’ diameters (h Dr). The term h is the counting efficiency of single ions.

A. BANTSAR AND S. PSZONA

been measured. The measured distributions are in good agreement with MC modelling. The comparison of the yield of cluster sizes (experiment in nitrogen) with the yield of complex damage to DNA (based on calculation in liquid water) shows an approximately similar dependence. ACKNOWLEDGEMENTS The authors thank to E. Jaworska and A. Dudzin´ski for their technical assistance during the experiments.

This work was supported partly by EMRP project SIB06. Figure 7. The mechanistic comparison of the measured ICSD for Dr equal to 0.32 and 0.66 mg cm22 with the yield of single and complex damages to DNA as calculated(1).

The following forms of DNA damages have been classified as SSB, SSBþ, DSB, DSBþ and DSBþþ. These forms of damage have been defined for several electron energies. For the purposes of this work, the data for 100 keV have been taken as close to the mean energy of electron spectrum of 131I, i.e. 190 keV. The working hypothesis which is applied for comparison purposes is that a cluster size equal to 1 can cause a single-strand breakage with probability given by the value of P1 of the ICSD. Consequently, for a given type of DNA breakage, the following cluster size has been assigned: (as an approximation) SSB-1; SSBþ-2; DSB-2; DSBþ-3; and for DSBþþ -4. The yield of SSBþ and DSB is given by P2, DSBþ is given by P3 and DSBþ is given by P4. The resulting mechanistic comparison is shown in Figure 7. Having in mind that in one side mechanistically the prediction was compared based on probability of energy clusters distribution by a mathematical model based on energy deposition with that predicted based on experimental ICSD. These two models are very different. The distribution of energy clusters in fact is based on assumption of a threshold (17.5 eV) for a single cluster. Basically the value 17.5 eV is not far from energy needed for forming ionisation in liquid water. This is a possible reason of some similarities in the shapes of the compared curves. At this moment, one can conclude that presented model based on experimentally derived ionisation cluster distribution could be used for the studies on track structure effects related to the complex damages to biological structures like DNA. CONCLUSIONS Ionisation cluster size distributions due to highenergy electrons emitted by a 131I radioactive source in nitrogen ‘to simulate DNA-like nanosites’ have

REFERENCES 1. Nikjoo, H., Bolton, C. E., Watanabe, R., Terrisol, M., O’Neill, P. and Goodhead, D. T. Modeling of DNA damage induced by energetic electrons (100 eV to 100 keV). Radiat. Prot. Dosim. 99, 77–80 (2002). 2. Pszona, S. A Track Ion Counter. In: Proc. 5th Symposium on microdosimetry, Report EUR 3452, pp. 1107–1121 (1974). 3. Pszona, S., Kula, J. and Marjanska, S. A new method for measuring ion clusters produced by charged particles in nanometre track section of DNA size. Nucl. Instrum. Methods Phys. Res. A447, 601–607 (2000). 4. Garty, G., Shchemelinin, S., Breskin, A., Chechik, R., Orion, I., Guedes, G. P., Schulte, R., Bashkirov, V. and Grosswendt, B. Wall-less Ion-counting nanodosimetry applied to protons. Radiat. Prot. Dosim. 99, 325–330 (2002). 5. De Nardo, L., Colautti, P., Baek, W. Y., Grosswendt, B., Alkaa, A., Se´gur, P. and Tornielli, G. Track nanodosimetry of an alpha particles. Radiat. Prot. Dosim. 99, 355– 358 (2002). 6. Bantsar, A., Grosswendt, B. and Pszona, S. Nanodosimetry of I-125 Auger electrons – experiment and modeling. Rad. Meas. 47, 1092–1096 (2012). 7. Bantsar, A., Grosswendt, B. and Pszona, S. Formation of ion clusters by low energy electrons in nanometric targets – experiment and Monte Carlo simulation. Radiat. Prot. Dosim. 122, 82–85 (2007). 8. Grosswendt, B., Pszona, S. and Bantsar, A. new descriptors of radiation quality based on nanodosimetry—a first approach. Radiat. Prot. Dosim. 126, 432 (2007). 9. Bantsar, A. Ionization cluster size distributions created by low energy electrons and alpha particles in nanometric track segment in gases. PhD Thesis. (2011). arXiv:1207.6893. 10. Grosswendt, B. From macro to nanodosimetry: limits of the absorbed-dose concept and definition of new quantities. In: Workshop on Uncertainty Assessment in Computational Dosimetry, Bologna, Italy, 8–10 October (2000). 11. Goodhead, D. T. Energy deposition stochasticsand track structure: what about the target? Radiat. Prot. Dosim. 122, 3– 15 (2006). 12. Pszona, S. and Kula, J. Ionization clusters at DNA level: experimental modeling. Radiat. Prot. Dosim. 99, 387– 390 (2002).

Page 4 of 4

Downloaded from http://rpd.oxfordjournals.org/ at North Dakota State University on May 19, 2015

FUNDING

Nanodosimetry of electrons: analysis by experiment and modelling.

Nanodosimetry experiments for high-energy electrons from a (131)I radioactive source interacting with gaseous nitrogen with sizes on a scale equivalen...
291KB Sizes 2 Downloads 8 Views