A Mathematical Model for the Effect of Low-Dose Radiation on the G2/M Transition

Carlos Contreras, Gustavo Carrero, Gerda de Vries

Research output: Contribution to journalJournal Articlepeer-review

3 Citations (Scopus)


We develop a mathematical model to study the immediate effect of low-dose radiation on the G2 checkpoint and the G2/M transition of the cell cycle via a radiation pathway (the ATM–Chk2 pathway) of an individual mammalian cell. The model consists of a system of nonlinear differential equations describing the dynamics of a network of regulatory proteins that play key roles in the G2/M transition, cell cycle oscillations, and the radiation pathway. We simulate the application of a single pulse of low-dose radiation at different intensities (∼ 0–0.4 Gy) and times during the latter part of the G2-phase. We use bifurcation analysis to characterize the effect of radiation on the G2/M transition via the ATM–Chk2 pathway. We show that radiation between 0.1 and 0.3 Gy can delay the G2/M transition, and radiation higher than 0.3 Gy can fully activate the G2 checkpoint. Also, our results show that radiation can be low enough to neither delay the G2/M transition nor activate the G2 checkpoint (∼ 0.1 Gy). Our model supports the idea that the cell response to radiation during G2-phase explains hyper-radiosensitivity and increased radioresistance (HRS/IRR) observed at low dose.

Original languageEnglish
Pages (from-to)3998-4021
Number of pages24
JournalBulletin of Mathematical Biology
Issue number10
Publication statusPublished - 1 Oct. 2019


  • ATM
  • Cell cycle modelling
  • Cell physiology
  • Chk2
  • G2 checkpoint
  • G2/M transition
  • HRS
  • IRR
  • Ionizing radiation
  • Radiation pathway
  • Regulatory dynamics


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