Derivation and experimental comparison of cell-division probability densities

J Theor Biol. 2014 Oct 21:359:129-35. doi: 10.1016/j.jtbi.2014.06.004. Epub 2014 Jun 12.

Abstract

Experiments have shown that, even in a homogeneous population of cells, the distribution of division times is highly variable. In addition, a homogeneous population of cells will exhibit a heterogeneous response to drug therapy. We present a simple stochastic model of the cell cycle as a multistep stochastic process. The model, which is based on our conception of the cell cycle checkpoint, is used to derive an analytical expression for the distribution of cell cycle times. We demonstrate that this distribution provides an accurate representation of cell cycle time variability and show how the model relates drug-induced changes in basic biological parameters to variability in response to drug treatment.

Keywords: First exit time; Intermitotic time; Mathematical modeling; Stochastic differential equation.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Cell Count
  • Cell Cycle / drug effects
  • Cell Cycle / physiology
  • Cell Division / drug effects
  • Cell Division / physiology*
  • Cell Proliferation / drug effects
  • Cycloheximide / pharmacology
  • Dimethyl Sulfoxide / pharmacology
  • Erlotinib Hydrochloride
  • Humans
  • Models, Theoretical*
  • Neoplasms / drug therapy
  • Neoplasms / pathology
  • Probability
  • Quinazolines / pharmacology
  • Stochastic Processes

Substances

  • Antineoplastic Agents
  • Quinazolines
  • Cycloheximide
  • Erlotinib Hydrochloride
  • Dimethyl Sulfoxide