title: Derivation and experimental comparison of cell-division probability densities.
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.
authors.affiliation: Department of Mathematical Sciences, Middle Tennessee State University, Murfreesboro, TN 37132, United States. Electronic address: rachel.leander@mtsu.edu.
authors.forename: R
authors.initials: R
authors.lastname: Leander
authors.affiliation: Department of Mathematics and Statistics, Texas Tech University, Lubbock, TX 79409, United States. Electronic address: edward.allen@ttu.edu.
authors.forename: E J
authors.initials: EJ
authors.lastname: Allen
authors.affiliation: Vanderbilt-Ingram Cancer Center, 771 Preston Building, 2220 Pierce Avenue, Nashville, TN 37232, United States. Electronic address: shawn.garbett@vanderbilt.edu.
authors.forename: S P
authors.initials: SP
authors.lastname: Garbett
authors.affiliation: Vanderbilt-Ingram Cancer Center, 771 Preston Building, 2220 Pierce Avenue, Nashville, TN 37232, United States. Electronic address: darren.tyson@vanderbilt.edu.
authors.forename: D R
authors.initials: DR
authors.lastname: Tyson
authors.affiliation: Vanderbilt-Ingram Cancer Center, 771 Preston Building, 2220 Pierce Avenue, Nashville, TN 37232, United States. Electronic address: vito.quaranta@vanderbilt.edu.
authors.forename: V
authors.initials: V
authors.lastname: Quaranta
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D002452:Cell Count; D002453:Cell Cycle / Q000187:drug effects / Q000502:physiology; D002455:Cell Division / Q000187:drug effects / Q000502:physiology*; D049109:Cell Proliferation / Q000187:drug effects; D003513:Cycloheximide / Q000494:pharmacology; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D000069347:Erlotinib Hydrochloride; D006801:Humans; D008962:Models, Theoretical; D009369:Neoplasms / Q000188:drug therapy / Q000473:pathology; D011336:Probability; D011799:Quinazolines / Q000494:pharmacology; D013269:Stochastic Processes
chemical_list: D000970:Antineoplastic Agents; D011799:Quinazolines; D003513:Cycloheximide; D000069347:Erlotinib Hydrochloride; D004121:Dimethyl Sulfoxide
keywords: First exit time; Intermitotic time; Mathematical modeling; Stochastic differential equation