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Modeling radiation-induced cell cycle delays

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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%.

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References

  • Amaldi U, Kraft G (2007) European developments in radiotherapy with beams of large radiobiological effectiveness. J Radiat Res (Tokyo) 48(Suppl A):27–41

    Article  Google Scholar 

  • 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 69:1673–1690

    Article  MATH  MathSciNet  Google Scholar 

  • 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):992–994

    Article  Google Scholar 

  • Cucinotta FA, Durante M (2006) Cancer risk from exposure to galactic cosmic rays: implications for space exploration by human beings. Lancet Oncol 7:431–435

    Article  Google Scholar 

  • Engen S, Lande R (1996) Population dynamic models generating the lognormal species abundance distribution. Math Biosci 132:169–183

    Article  MATH  Google Scholar 

  • 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 86:1510–1517

    Article  Google Scholar 

  • Feller W (1968) An introduction to probability theory and its applications. Wiley, New York

    MATH  Google Scholar 

  • Flatt P, Price J, Shaw A, Pietenpol J (1998) Differential cell cycle checkpoint response in normal human keratinocytes and fibroblasts. Cell Growth Differ 9:535–543

    Google Scholar 

  • Groesser T, Chun E, Rydberg B (2007) Relative biological effectiveness of high-energy iron ions for micronucleus formation at low doses. Radiat Res 168:675–682

    Article  Google Scholar 

  • 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 81:23–32

    Article  Google Scholar 

  • Hahnfeldt P, Hlatky L (1996) Resensitization due to redistribution of cells in phases of the cell cycle during arbitrary radiation protocols. Radiat Res 145:134–143

    Article  Google Scholar 

  • 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 8:119–124

    Google Scholar 

  • Kaufman G, Miller M, Savage J, Papworth D (1974) Chromosome aberration yields from multiple fixation regimes. J Theor Biol 44:91–103

    Article  Google Scholar 

  • Kohandel M, Kardar M, Milosevic M, Sivaloganathan S (2007) Dynamics of tumor growth and combination of anti-angiogenic and cytotoxic therapies. Phys Med Biol 52:3665–3677

    Article  Google Scholar 

  • 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 35:268–275

    Article  ADS  Google Scholar 

  • Li L, Zou L (2005) Sensing, signaling, and responding to DNA damage: organization of the checkpoint pathways in mammalian cells. J Cell Biochem 94:298–306

    Article  Google Scholar 

  • Mateuca R, Lombaert N, Aka PV, Decordier I, Kirsch-Volders M (2006) Chromosomal changes: induction, detection methods and applicability in human biomonitoring. Biochimie 88:1515–1531

    Article  Google Scholar 

  • 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 57:5877–5887

    Article  ADS  Google Scholar 

  • 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 628:56–66

    Google Scholar 

  • 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 69:275–282

    Google Scholar 

  • 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 69:155–166

    Article  Google Scholar 

  • 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 78:191–202

    Article  Google Scholar 

  • Scholz M (2003) Effects of ion radiation on cells and tissues. Adv Polym Sci 162:95–155

    Article  Google Scholar 

  • 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 66:59–75

    Article  Google Scholar 

  • Scholz M, Ritter S, Kraft G (1998) Analysis of chromosome damage based on the time course of aberrations. Int J Radiat Biol 74:325–331

    Article  Google Scholar 

  • Sinclair WK (1969) Protection by cysteamine against lethal X-ray damage during the cell cycle of Chinese hamster cells. Radiat Res 39:135–154

    Article  Google Scholar 

  • 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 83:501–513

    Article  Google Scholar 

  • Virgilio AD, Iwami K, Wätjen W, Kahl R, Degen G (2004) Genotoxicity of the isoflavones genistein, daidzein and equol in V79 cells. Toxicol Lett 151:151–162

    Article  Google Scholar 

  • 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 75:1357–1364

    Article  Google Scholar 

  • Wilson G (2007) Cell kinetics. Clin Oncol 19:370–384

    Article  Google Scholar 

  • Zaider M, Minerbo GN (1993) A mathematical model for cell cycle progression under continuous low-dose-rate irradiation. Radiat Res 133:20–26

    Article  Google Scholar 

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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.

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Correspondence to Anna Ochab-Marcinek.

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Ochab-Marcinek, A., Gudowska-Nowak, E., Nasonova, E. et al. Modeling radiation-induced cell cycle delays. Radiat Environ Biophys 48, 361–370 (2009). https://doi.org/10.1007/s00411-009-0239-7

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  • DOI: https://doi.org/10.1007/s00411-009-0239-7

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