title: Analysis of radiation-induced changes to human melanoma cultures using a mathematical model.
abstract: OBJECTIVE
  Tumour cells respond to ionizing radiation by cycle arrest, cell death or repair and possible regrowth. We have developed a dynamic mathematical model of the cell cycle to incorporate transition probabilities for entry into DNA replication and mitosis. In this study, we used the model to analyse effects of radiation on cultures of five human melanoma cell lines.
  
  
  METHODS
  Cell lines were irradiated (9 Gy) prior to further culture and harvesting at multiple points up to 96 h later. Cells were fixed, stained with propidium iodide and analysed for G(1)-, S- and G(2)/M-phase cells by flow cytometry. Data for all time points were fitted to a mathematical model. To provide unique solutions, cultures were grown in the presence and absence of the mitotic poison paclitaxel, added to prevent cell division.
  
  
  RESULTS
  The model demonstrated that irradiation at 9 Gy induced G(2)-phase arrest in all lines for at least 96 h. Two cell lines with wild-type p53 status additionally exhibited G(1)-phase arrest with recovery over 15 h, as well as evidence of cell loss. Resumption of cycling of surviving cells, as indicated by increases in G(1)/S and G(2)/M-phase transitions, was broadly comparable with results of clonogenic assays.
  
  
  CONCLUSIONS
  The results, combined with existing data from clonogenic survival assays, support the hypothesis that a dominant effect of radiation in these melanoma lines is the induction of long-term cell cycle arrest.
authors.affiliation: Auckland Cancer Society Research Centre, The University of Auckland, Auckland, New Zealand.
authors.forename: B
authors.initials: B
authors.lastname: Basse
authors.forename: W R
authors.initials: WR
authors.lastname: Joseph
authors.forename: E S
authors.initials: ES
authors.lastname: Marshall
authors.forename: B C
authors.initials: BC
authors.lastname: Baguley
mesh_terms: D002453:Cell Cycle / Q000528:radiation effects*; D045744:Cell Line, Tumor; D004261:DNA Replication / Q000528:radiation effects; D004273:DNA, Neoplasm / Q000737:chemistry; D005434:Flow Cytometry; D006801:Humans; D008545:Melanoma / Q000235:genetics* / Q000473:pathology; D008962:Models, Theoretical; D011839:Radiation, Ionizing; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D004273:DNA, Neoplasm; D016159:Tumor Suppressor Protein p53
references.citation: Cytometry. 1991;12(2):119-26
references.pmid: 1710959
references.citation: Oncol Res. 1993;5(8):301-9
references.pmid: 8012062
references.citation: Radiat Res. 2001 Jan;155(1 Pt 2):248-253
references.pmid: 11121242
references.citation: Science. 2003 Jun 6;300(5625):1542-8
references.pmid: 12791985
references.citation: Eur J Cancer. 1995;31A(2):230-7
references.pmid: 7718330
references.citation: EMBO J. 2003 Oct 15;22(20):5612-21
references.pmid: 14532133
references.citation: Cancer Res. 1996 Feb 15;56(4):840-7
references.pmid: 8631022
references.citation: Cancer Cell Int. 2001 Nov 23;1(1):1
references.pmid: 11983025
references.citation: Eur J Cancer. 1994;30A(9):1370-6
references.pmid: 7999427
references.citation: Oncol Res. 2000;12(3):149-55
references.pmid: 11216673
references.citation: Radiat Res. 2005 Jan;163(1):53-62
references.pmid: 15606307
references.citation: J Math Biol. 2004 Oct;49(4):329-57
references.pmid: 15657794
references.citation: Biochem Cell Biol. 2003 Jun;81(3):123-9
references.pmid: 12897845
references.citation: Cell Cycle. 2007 Apr 15;6(8):943-50
references.pmid: 17387280
references.citation: Math Biosci. 2008 May;213(1):40-9
references.pmid: 18433802
references.citation: J Math Biol. 2003 Oct;47(4):295-312
references.pmid: 14523574
references.citation: Bull Math Biol. 2005 Jul;67(4):815-30
references.pmid: 15893554
references.citation: Bull Math Biol. 2007 Jul;69(5):1673-90
references.pmid: 17361361
references.citation: Int J Radiat Oncol Biol Phys. 2004 Jul 15;59(4):928-42
references.pmid: 15234026
references.citation: Cytometry. 1989 Nov;10(6):695-705
references.pmid: 2582959
references.citation: Prog Biophys Mol Biol. 2004 Jun-Jul;85(2-3):353-68
references.pmid: 15142752
references.citation: Cancer Res. 1996 Feb 15;56(4):816-25
references.pmid: 8631019