A Model of Chromosome Aberration Induction: Applications to Space Research

Abstract Ballarini, F. and Ottolenghi, A. A Model of Chromosome Aberration Induction: Applications to Space Research. Radiat. Res. 164, 567–570 (2005). A mechanistic model and Monte Carlo code simulating chromosome aberration induction in human lymphocytes is presented. The model is based on the assumption that aberrations arise from clustered DNA lesions and that only the free ends of clustered lesions created in neighboring chromosome territories or in the same territory can join and produce exchanges. The lesions are distributed in the cell nucleus according to the radiation track structure. Interphase chromosome territories are modeled as compact intranuclear regions with volumes proportional to the chromosome DNA contents. Both Giemsa staining and FISH painting can be simulated, and background aberrations can be taken into account. The good agreement with in vitro data provides validation of the model in terms of both the assumptions adopted and the simulation techniques. As an application in the field of space research, the model predictions were compared with aberration yields measured among crew members of long-term missions on board Mir and ISS, assuming an average radiation quality factor of 2.4. The agreement obtained also validated the model for in vivo exposure scenarios and suggested possible applications to the prediction of other relevant aberrations, typically translocations.

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

[2]  F Ianzini,et al.  Direct comparison of biological effectiveness of protons and alpha-particles of the same LET. II. Mutation induction at the HPRT locus in V79 cells. , 1992, International journal of radiation biology.

[3]  M. Durante.  Biomarkers of Space Radiation Risk , 2005, Radiation research.

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

[5]  Marco Durante,et al.  The quality of DNA double-strand breaks: A Monte Carlo simulation of the end-structure of strand breaks produced by protons and alpha particles , 1995, Radiation and environmental biophysics.

[6]  R. Nagele,et al.  Chromosomes exhibit preferential positioning in nuclei of quiescent human cells. , 1999, Journal of cell science.

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

[8]  M. Sullenberger,et al.  Models and simulations , 1984 .

[9]  F. Ballarini,et al.  Models of chromosome aberration induction: an example based on radiation track structure , 2004, Cytogenetic and Genome Research.

[10]  M. Durante,et al.  Risk Estimation Based on Chromosomal Aberrations Induced by Radiation , 2001, Radiation research.

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

[12]  Michal Kozubek,et al.  3D Structure of the human genome: order in randomness , 2002, Chromosoma.

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

[14]  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.

[15]  L. Mullenders,et al.  Impact of radiation quality on the spectrum of induced chromosome exchange aberrations , 2001, International journal of radiation biology.

[16]  C. Eaves,et al.  Defective regulation of leukemic hematopoiesis in chronic myeloid leukemia. , 1998, Leukemia research.

[17]  D. Lloyd,et al.  The 60Co gamma ray dose-response for chromosomal aberrations in human lymphocytes analysed by FISH; applicability to biological dosimetry. , 1999, International journal of radiation biology.

[18]  F. Mitelman,et al.  Recurrent chromosome aberrations in cancer. , 2000, Mutation research.

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

[20]  A Ottolenghi,et al.  Modelling chromosomal aberration induction by ionising radiation: the influence of interphase chromosome architecture. , 2001, Advances in space research : the official journal of the Committee on Space Research.

[21]  P. Lichter,et al.  Evidence for a nuclear compartment of transcription and splicing located at chromosome domain boundaries , 1993, Chromosome Research.

[22]  Order from Randomness , 2007, 0706.3785.