Measuring cytotoxicity: a new perspective on LC50

Anticancer Res. 2007 Jan-Feb;27(1A):35-8.

Abstract

Background: Cytotoxicity in cell culture is typically expressed as LC50 the concentration of a given agent which is lethal to 50% of the cells. This number is dependent on the incubation time with the agent. Previously, a two-term exponential model has been proposed to describe cell growth after a cytotoxic event: y(t) = k, * exp(-d(1)*t) + k2 * exp(d(2)*t). A dose-response relationship was observed between the parameter k2 in this formula and the concentration of the cytotoxic agent etoposide, in high-grade glioma cells was independent of incubation time.

Materials and methods: In order to test if the model can be applied more generally, DAOY medulloblastoma cells treated with MS275, a histone deacetylase inhibitor, were used.

Results: The observed data fit the model well.

Conclusion: The concentration at which k2 is reduced by 50% is called KC50. It provides a far better description of the cytotoxicity of an agent in a specific cell line than the traditional LC50.

MeSH terms

  • Antineoplastic Agents / pharmacokinetics
  • Antineoplastic Agents / pharmacology*
  • Benzamides / pharmacokinetics
  • Benzamides / pharmacology*
  • Cell Line, Tumor
  • Child, Preschool
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor / methods*
  • Humans
  • Male
  • Medulloblastoma / drug therapy*
  • Medulloblastoma / metabolism
  • Models, Biological*
  • Pyridines / pharmacokinetics
  • Pyridines / pharmacology*

Substances

  • Antineoplastic Agents
  • Benzamides
  • Pyridines
  • entinostat