The role of DT-diaphorase in determining the sensitivity of human tumor cells to tirapazamine (SR 4233)

Int J Radiat Oncol Biol Phys. 1994 May 15;29(2):369-72. doi: 10.1016/0360-3016(94)90291-7.


Purpose: To determine the dependency of the aerobic and hypoxic toxicity of tirapazamine on the intracellular activity of DT-diaphorase.

Methods and materials: A panel of 18 human cell lines comprising predominantly small cell and nonsmall cell lung cancer and breast cancer lines were used. The activity of DT-diaphorase was determined in cytosolic preparations from cell lysates. The toxicity of tirapazamine was determined using the MTT assay after either 96 or 3 h aerobic exposure or 3 h treatment in hypoxia.

Results: The cell lines exhibited a 5000-fold range in DT-diaphorase activity. In toxicity experiments, values of IC50 range from 10.2-120 microM and from 155-1230 for 96 and 3 h aerobic exposures, respectively. In N2, IC50s ranged from 8-55 microM. None of the toxicity values correlate with activity of DT-diaphorase, neither did the ratio of aerobic:hypoxic toxicity (differential toxicity).

Conclusion: The expression of DT-diaphorase in human tumor cells does not affect the toxicity of tirapazamine.

Publication types

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

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Humans
  • NAD(P)H Dehydrogenase (Quinone) / physiology*
  • Radiation-Sensitizing Agents / pharmacology*
  • Tetrazolium Salts / metabolism
  • Thiazoles / metabolism
  • Tirapazamine
  • Triazines / pharmacology*
  • Tumor Cells, Cultured / drug effects*


  • Antineoplastic Agents
  • Radiation-Sensitizing Agents
  • Tetrazolium Salts
  • Thiazoles
  • Triazines
  • Tirapazamine
  • NAD(P)H Dehydrogenase (Quinone)
  • thiazolyl blue