Computer Simulation of Short DNA Fragments Induced by HIGH-LET Charged Particles

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Abstract

The formation of short DNA fragments, up to 3 kbp, induced in chromatin by nitrogen (LET 97 keV/mм) and iron (LET 190 keV/mм) ions was studied by computer simulation. Chromatin models with different structure parameters and Monte Carlo track structure simulation were used to assess the impact of chromatin fiber structure and LET on the DNA fragment size distribution. For the structures modeled (different types of solenoids, a chain of nucleosomes), the fragment size distribution had a maximum in the region of ~100 bp corresponding to the formation of DNA breaks in two neighboring turns of the helix on the nucleosome. The calculation predicted the peak in the region of ~1000 bp, corresponding to the formation of DNA breaks in two neighboring turns of the solenoid, which parameters depended on the degree of compactness of the fiber and were independent of LET. The assumption was introduced of the presence of subpopulations of various chromatin structures under irradiation. It allowed to explain the experimentally observed size distributions of the short DNA fragments induced by high-LET charged particles.

About the authors

Y. A Eidelman

N.M. Emanuel Institute of Biochemical Physics; National Research Nuclear University MEPhI

Moscow, Russia; Moscow, Russia

I. V Salnikov

N.M. Emanuel Institute of Biochemical Physics

Moscow, Russia

S. G Andreev

N.M. Emanuel Institute of Biochemical Physics; National Research Nuclear University MEPhI

Email: andreev_sg@mail.ru
Moscow, Russia; Moscow, Russia

References

  1. Chepel V. Yu., Khvostunov I. K., Mirny L. A., Talyzina T. A., and Andreev S. G. Computer model of condensed chromatin fiber for radiation damage simulation. In Abstr. Book of the Eleventh Symposium on Microdosimetry (Gatlinburg, Tennessee, USA, 1992), p. 22.
  2. Khvostunov I. K., Chepel V. Yu. and Andreev S. G. Calculation of DNA and chromatin breaks for low LET irradiation. In Abstr. Book of the 24-th Annual Meeting of the European Society for Radiation Biology, (Erfurt, Germany, 1992), p. 165.
  3. Chepel V. Yu., Khvostunov I. K., Mirny L. A., Talyzina T. A., and Andreev S. G. 3-D computer modelling of chromatin fibres for radiation damage simulation. Radiat. Prot. Dosim., 52 (1–4), 259–263 (1994). doi: 10.1093/oxfordjournals.rpd.a082197
  4. Khvostunov I. K., Andreev S. G., Pitkevich V. A., and Chepel V. Yu. Novel algorithm for analysis of DNA and chromatin damage induced by ionising radiation with different quality. In Proc. 10th Int. Congr. Radiation Research, Ed. by U. Hagen, D. Harder, H. Jung, and C. S. Streffer. (Wurzburg, 1995), v. 2, pp. 254–257.
  5. Holley W. R. and Chatterjee A. Theoretical modeling of radiation induced damage to chromatin. In Proc. 10th Int. Congr. Radiation Research, Ed. by U. Hagen, D. Harder, H. Jung, and C. S. Streffer. (Wurzburg, 1995), v. 2, pp. 249–253.
  6. Holley W. R. and Chatterjee A. Clusters of DNA damage induced by ionizing radiation: Formation of short DNA fragments. I. Theoretical modeling. Radiat. Res., 45 (2), 188–199 (1996). doi: 10.2307/3579174
  7. Андреев С. Г., Хвостунов И. К., Спитковский Д. М. и Талызина Т. А. Биофизическое моделирование радиационных повреждений ДНК и хроматина, индуцированных излучением разного качества. Радиац. биология. Радиоэкология, 37 (4), 533 (1997).
  8. Rydberg B., Holley W. R., Mian I. S., and Chatterjee A.. Chromatin conformation in living cells: support for a zig-zag model of the 30 nm chromatin fiber. J. Mol. Biol., 284 (1), 71–84 (1998). doi: 10.1006/jmbi.1998.2150
  9. Friedland W., Jacob P., Bernhardt P., Paretzke H. G., and Dingfelder M. Simulation of DNA damage after proton irradiation. Radiat. Res., 159 (3), 401–410 (2003). doi: 10.1667/0033-7587(2003)159[0401:soddap]2.0.co;2
  10. Friedland W., Dingfelder M., Kundrát P., and Jakob P. Track structures, DNA targets and radiation effects in the biophysical Monte Carlo simulation code PARTRAC. Mutat. Res. Mol. Mech. Mutagen., 711 (1– 2), 28–40 (2011). doi: 10.1016/j.mrfmmm.2011.01.003
  11. Tang N., Bueno M., Meylan S., Incerti S., Tran H. N., Vaurijoux A., Gruel G., and Villagrasa C. Influence of chromatin compaction on simulated early radiation-induced DNA damage using Geant4-DNA. Med. Phys., 46 (3), 1501 (2019). doi: 10.1002/mp.13405
  12. Shin W., Sakata D., Lampe N., Belov O., Tran N. H., Petrovic I., Ristic-Fira A., Dordevic M., Bernal M. A., Bordage M. C. , Francis Z., Kyriakou I., Perrot Y., Sasaki T., Villagrasa C., Guatelli S., Breton V., Emfietzoglou D., and Incerti S. A Geant4-DNA evaluation of radiation-induced DNA damage on a human fibroblast. Cancers, 13 (19), 4940 (2021). doi: 10.3390/cancers13194940
  13. Bertolet A., Ramos-Méndez J., McNamara A., Yoo D., Ingram S., Henthorn N., Warmenhoven J.-W., Faddegon B., Merchant M., McMahon S. J., Paganetti H., and Schuemann J. Impact of DNA geometry and scoring on Monte Carlo track-structure simulations of initial radiation-induced damage. Radiat. Res., 198 (3), 207 (2022). doi: 10.1667/RADE-21-00179.1
  14. Zhu K., Wu C., Peng X., Ji X., Luo S., Liu Y., Wang X. Nanoscale calculation of proton-induced DNA damage using a chromatin geometry model with Geant4-DNA. Int. J. Mol. Sci., 23 (11), 6343 (2022). doi: 10.3390/ijms23116343
  15. Khvostunov I. K. and Andreev S. G. Microdosimetric distributions for target volumes of complex topology. In Microdosimetry: an interdisciplinaty approach, Ed. by D.T. Goodhead, P.O’Neill, and H.G. Menzel (The Royal Society of Chemistry, Cambridge, 1997), pp. 47–50.
  16. Andreev S. G., Khvostunov I. K., Spitkovsky D. M., and Chepel V. Yu. Clustering of DNA breaks in chromatin fibre: dependence on radiation quality. In Microdosimetry: an interdisciplinaty approach, Ed. by D. T. Goodhead, P. O’Neill, and H. G. Menzel (The Royal society of Chemistry, Cambridge, 1997), pp. 133–136.
  17. Zhu H., McNamara A. L., McMahon S. J., RamosMendez J., Henthorn N. T., Faddegon B., Held K. D., Perl J., Li J., Paganetti H., and Schuemann J.. Cellular response to proton irradiation: A simulation study with TOPAS-nBio. Radiat. Res., 194 (1), 9 (2020). doi: 10.1667/RR15531.1
  18. Newman H. C., Prise K. M., Folkard M., and Michael B. D. DNA double-strand break distributions in X-ray and alpha-particle irradiated V79 cells: evidence for non-random breakage. Int. J. Radiat. Biol., 71 (4), 347 (1997). doi: 10.1080/095530097143978
  19. Stenerlow B., Hoglund E., Carlsson J., and Blomquist E. Rejoining of DNA fragments produced by radiations of different linear energy transfer. Int. J. Radiat. Biol., 76 (4), 549 (2000). doi: 10.1080/095530000138565
  20. Belli M., Cherubini R., Dalla Vecchia M., Dini V., Esposito G., Moschini G., Sapora O., Signoretti C., Simone G., Sorrentino E., and Tabocchini M. A. DNA fragmentation in mammalian cells exposed to various light ions. Adv. Space Res., 27 (2), 393 (2001). doi: 10.1016/s0273-1177(01)00007-2
  21. Pinto M., Prise K. M., and Michael B. D. Quantification of radiation induced DNA double-strand breaks in human fibroblasts by PFGE: testing the applicability of random breakage models. Int. J. Radiat. Biol., 78 (5), 375 (2002). doi: 10.1080/09553000110110941
  22. Ponomarev A. L., Cucinotta F. A., Sachs R. K., and Brenner D. J. Monte Carlo predictions of DNA fragment-size distributions for large sizes after HZE particle irradiation. Phys. Med., 17, 153 (2001).
  23. Khvostunov I. K., Andreev S. G., and Yu. A. Eidelman. Biophysical analysis of radiation induced initial DNA fragmentation. Radiat. Prot. Dosim., 99 (1–4), 151 (2002). doi: 10.1093/oxfordjournals.rpd.a006748
  24. Fakir H., Sachs R. K., Stenerlow B., and Hofmann W. Clusters of DNA double-strand breaks induced by different doses of nitrogen ions for various LETs: experimental measurements and theoretical analyses. Radiat. Res., 166 (6), 917 (2006). doi: 10.1667/RR0639.1
  25. Rydberg B. Clusters of DNA damage induced by ionizing radiation: formation of short DNA fragments. II. Experimental detection. Radiat. Res., 145 (2), 200 (1996). doi: 10.2307/3579175
  26. Incerti S., Kyriakou I., Bernal M. A., Bordage M. C., Francis Z., Guatelli S., Ivanchenko V., Karamitros M., Lampe N., Lee S. B., Meylan S., Min C. H., Shin W. G., Nieminen P., Sakata D., Tang N., Villagrasa C., Tran H. N., and Brown J. M. C. Geant4-DNA example applications for track structure simulations in liquid water: A report from the Geant4-DNA Project. Med. Phys., e722 (2018). doi: 10.1002/mp.13048
  27. Эйдельман Ю. А., Сальников И. В. и Андреев С. Г. Анализ неопределенностей расчетов эффективности радиационных повреждений ДНК. Радиац. биология. Радиоэкология, 63 (1), 34 (2023). doi: 10.31857/S086980312301006X
  28. Charlton D. E., Nikjoo H. and Humm J. L. Calculation of initial yields of singleand double-strand breaks in cell nuclei from electrons, protons and alpha particles. Int. J. Radiat. Biol., 56 (1), 1 (1989). doi: 10.1080/09553008914551141
  29. Becker D. and Sevilla M. D. The chemical consequences of radiation damage to DNA. Adv. Radiat. Biol., 17, 121 (1993). doi: 10.1016/B978-0-12-035417-7.50006-4
  30. Risca V. I., Denny S. K., Straight A. F., and Greenleaf W. J. Variable chromatin structure revealed by in situ spatially correlated DNA cleavage mapping. Nature, 541 (7636), 237 (2017). doi: 10.1038/nature20781
  31. Finn E. H., Pegoraro G., Brandão H. B., Valton A.-L., Oomen M. E., Dekker J., Mirny L., and Misteli T. Extensive heterogeneity and intrinsic variation in spatial genome organization. Cell, 176 (6), 1502.e10 (2019). doi: 10.1016/j.cell.2019.01.020
  32. Eidelman Y., Salnikov I., Slanina S., and Andreev S.. Chromosome folding promotes intrachromosomal aberrations under radiationand nuclease-induced DNA breakage. Int. J. Mol. Sci., 22 (22), 12186 (2021). doi: 10.3390/ijms222212186

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