Advertisement

Modeling radiation-induced cell cycle delays

  • Anna Ochab-MarcinekEmail author
  • Ewa Gudowska-Nowak
  • Elena Nasonova
  • Sylvia Ritter
Original Paper

Abstract

Ionizing radiation is known to delay the cell cycle progression. In particular after particle exposure significant delays have been observed and it has been shown that the extent of delay affects the expression of damage, such as chromosome aberrations. Thus, to predict how cells respond to ionizing radiation and to derive reliable estimates of radiation risks, information about radiation-induced cell cycle perturbations is required. In the present study we describe and apply a method for retrieval of information about the time-course of all cell cycle phases from experimental data on the mitotic index only. We study the progression of mammalian cells through the cell cycle after exposure. The analysis reveals a prolonged block of damaged cells in the G2 phase. Furthermore, by performing an error analysis on simulated data valuable information for the design of experimental studies has been obtained. The analysis showed that the number of cells analyzed in an experimental sample should be at least 100 to obtain a relative error <20%.

Keywords

Cell Cycle Progression Mitotic Index Cell Cycle Phase Current Phase Duration Distribution 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgments

This work was supported in part (A. O-M) by the grant of Polish State Committee for Scientific Research (KBN, Grant No 1 P03B 159 29). Moreover, E. G-N acknowledges Marie Curie TOK COCOS grant at the Mark Kac Complex Systems Research Center in Kraków, Poland. E.N. was supported by BMBF (Bonn, Germany) under contract number 02S8203 and 02S8497.

References

  1. Amaldi U, Kraft G (2007) European developments in radiotherapy with beams of large radiobiological effectiveness. J Radiat Res (Tokyo) 48(Suppl A):27–41CrossRefGoogle Scholar
  2. Basse B, Ubezio P (2007) A generalised age- and phase-structured model of human tumour cell populations both unperturbed and exposed to a range of cancer therapies. Bull Math Biol 69:1673–1690zbMATHCrossRefMathSciNetGoogle Scholar
  3. Chaung W, Mi LJ, Boorstein RJ (1997) The p53 status of Chinese hamster V79 cells frequently used for studies on DNA damage and DNA repair. Nucleic Acid Res 25(5):992–994CrossRefGoogle Scholar
  4. Cucinotta FA, Durante M (2006) Cancer risk from exposure to galactic cosmic rays: implications for space exploration by human beings. Lancet Oncol 7:431–435CrossRefGoogle Scholar
  5. Engen S, Lande R (1996) Population dynamic models generating the lognormal species abundance distribution. Math Biosci 132:169–183zbMATHCrossRefGoogle Scholar
  6. Erba E, Bassano L, Liberti GD, Muradore I, Chiorino G, Ubezio P, Vignati S, Codegoni A, Desiderio MA, Faircloth G (2002) Cell cycle phase perturbations and apoptosis in tumour cells induced by aplidine. Br J Cancer 86:1510–1517CrossRefGoogle Scholar
  7. Feller W (1968) An introduction to probability theory and its applications. Wiley, New YorkzbMATHGoogle Scholar
  8. Flatt P, Price J, Shaw A, Pietenpol J (1998) Differential cell cycle checkpoint response in normal human keratinocytes and fibroblasts. Cell Growth Differ 9:535–543Google Scholar
  9. Groesser T, Chun E, Rydberg B (2007) Relative biological effectiveness of high-energy iron ions for micronucleus formation at low doses. Radiat Res 168:675–682CrossRefGoogle Scholar
  10. Gudowska-Nowak E, Kleczkowski A, Nasonova E, Scholz M, Ritter S (2005) Correlation between mitotic delay and aberration burden, and their role for the analysis of chromosome damage. Int J Radiat Biol 81:23–32CrossRefGoogle Scholar
  11. Hahnfeldt P, Hlatky L (1996) Resensitization due to redistribution of cells in phases of the cell cycle during arbitrary radiation protocols. Radiat Res 145:134–143CrossRefGoogle Scholar
  12. Hartmann N, Gilbert C, Jansson B, Macdonald PDM, Steel G, Valleron A (1975) A comparison of computer methods for the analysis of fraction labelled mitoses curves. Cell Tissue Kinet 8:119–124Google Scholar
  13. Kaufman G, Miller M, Savage J, Papworth D (1974) Chromosome aberration yields from multiple fixation regimes. J Theor Biol 44:91–103CrossRefGoogle Scholar
  14. Kohandel M, Kardar M, Milosevic M, Sivaloganathan S (2007) Dynamics of tumor growth and combination of anti-angiogenic and cytotoxic therapies. Phys Med Biol 52:3665–3677CrossRefGoogle Scholar
  15. Lee R, Nasonova E, Ritter S (2005) Chromosome aberration yields and apoptosis in human lymphocytes irradiated with Fe-ions of differing LET. Adv Space Res 35:268–275CrossRefADSGoogle Scholar
  16. Li L, Zou L (2005) Sensing, signaling, and responding to DNA damage: organization of the checkpoint pathways in mammalian cells. J Cell Biochem 94:298–306CrossRefGoogle Scholar
  17. Mateuca R, Lombaert N, Aka PV, Decordier I, Kirsch-Volders M (2006) Chromosomal changes: induction, detection methods and applicability in human biomonitoring. Biochimie 88:1515–1531CrossRefGoogle Scholar
  18. Montalenti F, Sena G, Capella P, Ubezio P (1998) Simulating cancer cell kinetics after drug treatment: application to cisplatin on ovarian carcinoma. Phys Rev E 57:5877–5887CrossRefADSGoogle Scholar
  19. Pathak R, Dey S, Sarma A, Khuda-Bukhsh A (2007) Genotoxic effects in M5 cells and Chinese hamster V79 cells after exposure to 7Li-beam (LET=60 kev/micron) and correlation of their survival dynamics to nuclear damages and cell death. Mutat Res 628:56–66Google Scholar
  20. Purrot R, Vulpis N, Lloyd D (1980) The use of harlequin staining to measure delay in the human lymphocyte cell cycle induced by in vitro X-irradiation. Mutat Res 69:275–282Google Scholar
  21. Ritter S, Nasonova E, Scholz M, Kraft-Weyrather W, Kraft G (1996) Comparison of chromosomal damage induced by X-rays and Ar ions with an LET of 1840 kev/μm in G1 V79 cells. Int J Radiat Biol 69:155–166CrossRefGoogle Scholar
  22. Ritter S, Nasonova E, Gudowska-Nowak E (2000) Effect of LET on the yield and the quality chromosomal damage in metaphase cells: a time-course study. Int J Radiat Biol 78:191–202CrossRefGoogle Scholar
  23. Scholz M (2003) Effects of ion radiation on cells and tissues. Adv Polym Sci 162:95–155CrossRefGoogle Scholar
  24. Scholz M, Kraft-Weyrather W, Ritter S, Kraft G (1994) Cell cycle delays induced by heavy ion irradiation of synchronous mammalian cells. Int J Radiat Biol 66:59–75CrossRefGoogle Scholar
  25. Scholz M, Ritter S, Kraft G (1998) Analysis of chromosome damage based on the time course of aberrations. Int J Radiat Biol 74:325–331CrossRefGoogle Scholar
  26. Sinclair WK (1969) Protection by cysteamine against lethal X-ray damage during the cell cycle of Chinese hamster cells. Radiat Res 39:135–154CrossRefGoogle Scholar
  27. Tenhumberg S, Gudowska-Nowak E, Nasonova E, Ritter S (2007) Cell cycle arrest and aberration yield in normal human fibroblasts. II: effects of 11 MeV u−1 C ions and 9.9 MeV u−1 Ni ions. Int J Radiat Biol 83:501–513CrossRefGoogle Scholar
  28. Virgilio AD, Iwami K, Wätjen W, Kahl R, Degen G (2004) Genotoxicity of the isoflavones genistein, daidzein and equol in V79 cells. Toxicol Lett 151:151–162CrossRefGoogle Scholar
  29. Weyrather W, Ritter S, Scholz M, Kraft G (1999) RBE for carbon track-segment irradiation in cell lines of differing repair capacity. Int J Radiat Biol 75:1357–1364CrossRefGoogle Scholar
  30. Wilson G (2007) Cell kinetics. Clin Oncol 19:370–384CrossRefGoogle Scholar
  31. Zaider M, Minerbo GN (1993) A mathematical model for cell cycle progression under continuous low-dose-rate irradiation. Radiat Res 133:20–26CrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Anna Ochab-Marcinek
    • 1
    • 2
    Email author
  • Ewa Gudowska-Nowak
    • 2
    • 3
    • 4
  • Elena Nasonova
    • 4
    • 5
  • Sylvia Ritter
    • 4
  1. 1.Department of Soft Condensed Matter, Institute of Physical ChemistryPolish Academy of SciencesWarsawPoland
  2. 2.Marian Smoluchowski Institute of PhysicsJagiellonian UniversityKrakowPoland
  3. 3.Mark Kac Complex Systems Research CentreJagiellonian UniversityKrakowPoland
  4. 4.Biophysics DepartmentGesellschaft für Schwerionenforschung (GSI)DarmstadtGermany
  5. 5.Joint Institute for Nuclear Research (JINR)Dubna, MoscowRussia

Personalised recommendations