Chromosome Aberrations by Heavy Ions
It is well known that mammalian cells exposed to ionizing radiation can show different types of chromosome aberrations (CAs) including dicentrics, translocations, rings, deletions and complex exchanges. Chromosome aberrations are a particularly relevant endpoint in radiobiology, because they play a fundamental role in the pathways leading either to cell death, or to cell conversion to malignancy. In particular, reciprocal translocations involving pairs of specific genes are strongly correlated (and probably also causally-related) with specific tumour types; a typical example is the BCR-ABL translocation for Chronic Myeloid Leukaemia. Furthermore, aberrations can be used for applications in biodosimetry and more generally as biomarkers of exposure and risk, that is the case for cancer patients monitored during Carbon-ion therapy and astronauts exposed to space radiation. Indeed hadron therapy and astronauts’ exposure to space radiation represent two of the few scenarios where human beings can be exposed to heavy ions. After a brief introduction on the main general features of chromosome aberrations, in this work we will address key aspects of the current knowledge on chromosome aberration induction, both from an experimental and from a theoretical point of view. More specifically, in vitro data will be summarized and discussed, outlining important issues such as the role of interphase death/mitotic delay and that of complex-exchange scoring. Some available in vivo data on cancer patients and astronauts will be also reported, together with possible interpretation problems. Finally, two of the few available models of chromosome aberration induction by ionizing radiation (including heavy ions) will be described and compared, focusing on the different assumptions adopted by the authors and on how these models can deal with heavy ions.
KeywordsChromosome Aberration International Space Station Complex Exchange Relative Biological Effectiveness Chromosome Territory
This work was partially supported by EU (“RISC-RAD” project, Contract no. FI6R-CT-2003-508842, and “NOTE” project, Contract no. FI6R-036465) and ASI (Italian Space Agency, “Mo-Ma/COUNT” project).
- 1.Savage J, Simpson P, Mutat Res 312, 51–60 (1994)Google Scholar
- 9.Bonassi S, Hagmar L, Stromberg U, Huici Montagud A, Tinnerberg H, Forni A, Heikkila P, Wanders S, Norppa H, for the European Study Group on Cytogenetic Biomarkers and Health (ESCH), Cancer Res 60, 1619–1625 (2000)Google Scholar
- 12.Sakamoto-Hojo E, Natarajan AT, Curado MP, Radiat Prot Dosim 86, 25–32 (1999)Google Scholar
- 17.Johnson K, Nath J et al., Mutat Res 439, 77–85 (1999)Google Scholar
- 23.Yang T, George K, Johnson AS, Durante M, Fedorenko BS, Biodosimetry results from space flight MIR-18 Radiat Res 148, S17–S23 (1997)Google Scholar
- 29.Kolb H, Bone marrow morbidity of radiotherapy. In: Plowman P, McElwain T, Meadows A (eds) Complications of cancer management, Oxford, pp 398–410 (1991)Google Scholar
- 30.Durante M, La Rivista del Nuovo Cimento 19(12),1–44 (1996)Google Scholar
- 46.Lea DE, Actions of radiations on living cells. Cambridge University Press, Cambridge, UK (1946)Google Scholar
- 54.Ballarini F, Ottolenghi A, Radiat Environ Biophys 43 (2004)Google Scholar
- 56.Ballarini F, Biaggi M, Ottolenghi A, Radiat Prot Dosim 99, 175–182 (2002)Google Scholar
- 57.Ballarini F, Battistoni G, Cerutti F et al., Physics to understand biology: Monte Carlo approaches to investigate space radiation doses and their effects on DNA and chromosomes. In: Gadioli E (ed) Proc of the 11th International conference on nuclear reaction mechanisms, Varenna, Italy, June 12–16, 2006. Ricerca Scientifica ed Educazione Permanente suppl 126, pp 591–600 (2006)Google Scholar
- 59.F. Ballarini, M.V. Garzelli, G. Givone, A. Mairani, A. Ottolenghi, D. Scannicchio, S. Trovati, A. Zanini (2008), Proc Int Conf on Nuclear Data for Science and Technology 2007, Nice, France, April 2007, vol. 2, pp 1337–1341 (pdf available at http://nd2007.edpsciences.org)