Quantitative measure of cytotoxicity of anticancer drugs and other agents

Zhimin Tao, Eyone Jones, Jerry Goodisman, Abdul Kader Souid

Research output: Contribution to journalArticlepeer-review

20 Citations (Scopus)

Abstract

Many anticancer drugs act on cancer cells to promote apoptosis, which includes impairment of cellular respiration (mitochondrial O2 consumption). Other agents also inhibit cellular respiration, sometimes irreversibly. To investigate the sensitivity of cancer cells to cytotoxins, including anticancer drugs, we compare the profiles of cellular O2 consumption in the absence and presence of these agents. Oxygen measurements are made at 37 °C, using glucose as a substrate, with [O2] obtained from the phosphorescence decay rate of a palladium phosphor. The rate of respiration k is defined as -d[O2]/dt in a sealed container. Different toxins produce different profiles of impaired respiration, implying different mechanisms for the drug-induced mitochondrial dysfunction. The decrease in the average value of k over a fixed time period, I, is proposed as a characteristic value to assess mitochondrial injury. The value of I depends on the nature of the toxin, its concentration, and the exposure time as well as on the cell type. Results for several cell types and 10 cytotoxins are presented here.

Original languageEnglish
Pages (from-to)43-52
Number of pages10
JournalAnalytical Biochemistry
Volume381
Issue number1
DOIs
Publication statusPublished - Oct 1 2008
Externally publishedYes

Keywords

  • Cytotoxicity
  • Oxygen consumption
  • Phosphorescence
  • Respiration

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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