Dosing metric in cellular experiments: The mol/cell metric has its limitations

Toxicol In Vitro. 2022 Feb:78:105272. doi: 10.1016/j.tiv.2021.105272. Epub 2021 Nov 2.

Abstract

It has been argued that the mol/cell metric is more universal than concentration of the toxic agent since in many cases the effect of dose expressed as mol/cell is independent of ex-perimental setup. We confirmed it for hemolysis of erythrocytes in phosphate-buffered saline induced by hypochlorite where the amount of femtomoles/cell of hypochlorite needed for 50% hemolysis was independent of erythrocyte concentration. However, in the presence of blood plasma this metric became dependent on cell concentration. Similarly, the effect of 3-bromopyruvic acid (3-BP) on PEO1 cells as a function of mol/cell ratio depended on the volume of the 3-BP containing medium, due to the reaction of 3-BP with components of the medium. Hemolytic amounts of sodium dodecyl sulfate and Triton X-100 expressed as mol/cell decreased with increasing cell concentration while the effect of DMSO on the viability of a constant number of fibroblasts was independent of the volume of DMSO-containing medium. These results demonstrate that the mol/cell metric is still dependent on experimental conditions when the toxic agent interacts with components of the medium or when its physical state is modified by the target cells, and the effect is independent of the mol/per cell ratio for high excess of a cell damaging agent.

Keywords: 3-Bromopyruvate; DMSO; Dose metric; Hemolysis; Hypochlorite; Mol/cell; Sodium dodecyl sulfate; Triton X-100.

MeSH terms

  • Cell Line
  • Cell Line, Tumor
  • Dimethyl Sulfoxide / administration & dosage
  • Dimethyl Sulfoxide / toxicity
  • Dose-Response Relationship, Drug*
  • Erythrocytes / drug effects*
  • Fibroblasts / drug effects*
  • Hemolysis / drug effects
  • Humans
  • Hypochlorous Acid / administration & dosage
  • Hypochlorous Acid / toxicity
  • Octoxynol / administration & dosage
  • Octoxynol / toxicity
  • Pyruvates / administration & dosage
  • Pyruvates / toxicity
  • Sodium Dodecyl Sulfate / administration & dosage
  • Sodium Dodecyl Sulfate / toxicity

Substances

  • Pyruvates
  • Sodium Dodecyl Sulfate
  • bromopyruvate
  • Hypochlorous Acid
  • Octoxynol
  • Dimethyl Sulfoxide