Heavy-ion effects: from track structure to DNA and chromosome damage

The use of carbon ions for the treatment of certain tumour types, especially radioresistant tumours, is becoming more frequent due to the carbon- ion dose localization and high relative biological effectiveness (RBE) in the Bragg peak region. Human beings can also be exposed to heavy ions in space, since galactic cosmic rays are a mixed field consisting of not only high-energy protons and He ions, but also heavier ions including iron. Due to their high linear energy transfer (LET), heavy ions have peculiar track structures, characterized by a high level of energy deposition clustering. Furthermore, high-energy ions produce energetic secondary electrons ('delta rays') which can give rise to energy depositions several micrometres away from the core of the primary particle track. Also in view of hadron therapy and space radiation applications, it is therefore important to characterize heavy-ion tracks from a physical and biophysical point of view. In this framework, herein we will discuss the main physical features of heavy-ion track structure, as well as heavy-ion-induced DNA double-strand breaks, which are regarded as one of the most important initial radiobiological lesions and chromosome aberrations, which are correlated both with cell death and with cell conversion to malignancy.

[1]  H. Paretzke,et al.  Monte Carlo simulation of the production of short DNA fragments by low-linear energy transfer radiation using higher-order DNA models. , 1998, Radiation research.

[2]  Andrea Ottolenghi,et al.  A model of chromosome aberration induction and chronic myeloid leukaemia incidence at low doses , 2004, Radiation and environmental biophysics.

[3]  M. Monobe,et al.  Induction of asymmetrical type of chromosomal aberrations in cultured human lymphocytes by ion beams of different energies at varying LET from HIMAC and RRC. , 1998, Advances in space research : the official journal of the Committee on Space Research.

[4]  B. Dutrillaux,et al.  Chromosomal aberrations induced in human lymphocytes by high-LET irradiation. , 1997, International journal of radiation biology.

[5]  Ugo Amaldi,et al.  European developments in radiotherapy with beams of large radiobiological effectiveness. , 2007, Journal of radiation research.

[6]  H. Ehrenreich,et al.  Self-Consistent Field Approach to the Many-Electron Problem , 1959 .

[7]  I. Sair Chromatin Conformation in Living Cells: Support for a Zig-Zag Model of the 30 nm Chromatin Fiber , 1998 .

[8]  R. H. Ritchie,et al.  PHYSICAL ASPECTS OF CHARGED PARTICLE TRACK STRUCTURE , 1989 .

[9]  M. Durante,et al.  Dose–response of initial G2-chromatid breaks induced in normal human fibroblasts by heavy ions , 2001, International journal of radiation biology.

[10]  T. Rabbitts,et al.  Chromosomal translocations in human cancer , 1994, Nature.

[11]  Marco Durante,et al.  Biological dosimetry in astronauts , 1996 .

[12]  J R Savage,et al.  A brief survey of aberration origin theories. , 1998, Mutation research.

[13]  Mariel Vazquez,et al.  Radiation-induced chromosome aberrations: insights gained from biophysical modeling. , 2002, BioEssays : news and reviews in molecular, cellular and developmental biology.

[14]  L Sabatier,et al.  Radiation-induced chromosome damage in astronauts' lymphocytes. , 1996, International Journal of Radiation Biology.

[15]  M. Löbrich,et al.  Non-random distribution of DNA double-strand breaks induced by particle irradiation. , 1996, International journal of radiation biology.

[16]  Peter Jacob,et al.  Simulation of DNA Damage after Proton Irradiation , 2003, Radiation Research.

[17]  G. Reitz,et al.  Chromosomal aberrations in blood lymphocytes of astronauts after long-term space flights. , 1997, International journal of radiation biology.

[18]  F A Cucinotta,et al.  Karyotypes of Human Lymphocytes Exposed to High-Energy Iron Ions , 2002, Radiation research.

[19]  B. Rydberg,et al.  Clusters of DNA damage induced by ionizing radiation: formation of short DNA fragments. II. Experimental detection. , 1996, Radiation research.

[20]  S. Ritter,et al.  Relationship between aberration yield and mitotic delay in human lymphocytes exposed to 200 MeV/u Fe-ions or X-rays. , 2002, Journal of radiation research.

[21]  D. Lea Actions of radiations on living cells. , 1955 .

[22]  M. Durante,et al.  Chromosome aberration dosimetry in cosmonauts after single or multiple space flights , 2004, Cytogenetic and Genome Research.

[23]  S. Ritter,et al.  Cytogenetic effects of densely ionising radiation in human lymphocytes: impact of cell cycle delays , 2004, Cytogenetic and Genome Research.

[24]  K. Prise,et al.  DNA double-strand break distributions in X-ray and alpha-particle irradiated V79 cells: evidence for non-random breakage. , 1997, International journal of radiation biology.

[25]  A. Mairani,et al.  Radiation risk estimation: Modelling approaches for “targeted” and “non-targeted” effects , 2007 .

[26]  F Ballarini,et al.  Modelling radiation-induced biological lesions: from initial energy depositions to chromosome aberrations , 1999, Radiation and environmental biophysics.

[27]  H. Paretzke,et al.  First steps towards systems radiation biology studies concerned with DNA and chromosome structure within living cells , 2008, Radiation and environmental biophysics.

[28]  A. Rubanovich,et al.  Cytogenetic studies of blood lymphocytes from cosmonauts after long-term space flights on Mir station. , 2001, Advances in space research : the official journal of the Committee on Space Research.

[29]  H. J. Brede,et al.  Induction of DNA double-strand breaks by 1H and 4He lons in primary human skin fibroblasts in the LET range of 8 to 124 keV/microm. , 1999, Radiation research.

[30]  A. Campa,et al.  DNA DSB induced in human cells by charged particles and gamma rays: Experimental results and theoretical approaches , 2005, International journal of radiation biology.

[31]  H. Schaefer,et al.  Microdosimetric structure of heavy ion tracks in tissue , 1976, Radiation and environmental biophysics.

[32]  E. Blakely,et al.  Chromosomal damage and repair in G1-phase Chinese hamster ovary cells exposed to charged-particle beams. , 1994, Radiation research.

[33]  M. Durante,et al.  Induction of chromosome aberrations in human cells by charged particles. , 1997, Radiation research.

[34]  D T Goodhead,et al.  Initial events in the cellular effects of ionizing radiations: clustered damage in DNA. , 1994, International journal of radiation biology.

[35]  D. Pines,et al.  The theory of quantum liquids , 1968 .

[36]  Andrea Ottolenghi,et al.  A Model of Chromosome Aberration Induction: Applications to Space Research , 2005, Radiation research.

[37]  A Ottolenghi,et al.  Chromosome aberrations induced by light ions: Monte Carlo simulations based on a mechanistic model. , 1999, International journal of radiation biology.

[38]  M. Durante,et al.  Biodosimetry of ionizing radiation by selective painting of prematurely condensed chromosomes in human lymphocytes. , 1997, Radiation research.

[39]  A Ottolenghi,et al.  Chromosome aberrations as biomarkers of radiation exposure: modelling basic mechanisms. , 2003, Advances in space research : the official journal of the Committee on Space Research.

[40]  M. Durante,et al.  Biodosimetry results from space flight Mir-18. , 1997, Radiation research.

[41]  A Ottolenghi,et al.  Nuclear architecture and radiation induced chromosome aberrations: models and simulations. , 2002, Radiation protection dosimetry.

[42]  A A Edwards,et al.  The use of chromosomal aberrations in human lymphocytes for biological dosimetry. , 1997, Radiation research.

[43]  M. Durante,et al.  X-rays vs. carbon-ion tumor therapy: cytogenetic damage in lymphocytes. , 2000, International journal of radiation oncology, biology, physics.

[44]  M. Durante,et al.  Rejoining and misrejoining of radiation-induced chromatin breaks. IV. Charged particles. , 1998, Radiation research.

[45]  L. Hedin,et al.  Effects of Electron-Electron and Electron-Phonon Interactions on the One-Electron States of Solids , 1969 .

[46]  Herwig G. Paretzke,et al.  Inelastic-collision cross sections of liquid water for interactions of energetic protons , 2000 .

[47]  G. Moschini,et al.  DNA fragmentation in V79 cells irradiated with light ions as measured by pulsed-field gel electrophoresis. I. Experimental results , 2002, International journal of radiation biology.

[48]  M. Durante,et al.  Biological Effectiveness of Accelerated Particles for the Induction of Chromosome Damage Measured in Metaphase and Interphase Human Lymphocytes , 2003, Radiation research.

[49]  E. M. Lifshitz,et al.  Electrodynamics of continuous media , 1961 .

[50]  T. Kawata,et al.  High- and low-LET induced chromosome damage in human lymphocytes: a time-course of aberrations in metaphase and interphase , 2001, International journal of radiation biology.

[51]  A. Campa,et al.  Modeling of DNA fragmentation induced in human fibroblasts by 56Fe ions , 2007 .

[52]  M. Durante,et al.  Association between G2-phase block and repair of radiation-induced chromosome fragments in human lymphocytes. , 1999, Radiation research.

[53]  A. Kleczkowski,et al.  Correlation between mitotic delay and aberration burden, and their role for the analysis of chromosomal damage , 2005, International journal of radiation biology.

[54]  F A Cucinotta,et al.  Chromosome Aberrations in the Blood Lymphocytes of Astronauts after Space Flight , 2001, Radiation research.

[55]  Aloke Chatterjee,et al.  Clusters of DNA Damage Induced by Ionizing Radiation: Formation of Short DNA Fragments. I. Theoretical Modeling , 1996 .

[56]  G. Reitz,et al.  Radiation measurements on the Mir Orbital Station. , 2002, Radiation measurements.

[57]  A. Campa,et al.  DNA fragmentation in V79 cells irradiated with light ions as measured by pulsed‐field gel electrophoresis. II. Simulation with a generalized broken stick model , 2004, International journal of radiation biology.

[58]  Herwig G. Paretzke,et al.  Electron inelastic-scattering cross sections in liquid water , 1999 .

[59]  A. Edwards Modelling radiation-induced chromosome aberrations , 2002, International journal of radiation biology.

[60]  D. Alloni Radiation biophysics modeling: track structure theoretical bases and Monte Carlo simulations of DNA damage , 2007 .

[61]  B. Stenerlöw,et al.  DNA damage induced by radiation of different linear energy transfer: initial fragmentation. , 2000, International journal of radiation biology.