title: The role of DT-diaphorase in determining the sensitivity of human tumor cells to tirapazamine (SR 4233).
abstract: OBJECTIVE
  To determine the dependency of the aerobic and hypoxic toxicity of tirapazamine on the intracellular activity of DT-diaphorase.
  
  
  METHODS
  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).
  
  
  CONCLUSIONS
  The expression of DT-diaphorase in human tumor cells does not affect the toxicity of tirapazamine.
authors.affiliation: MRC Radiobiology Unit, Chilton, Didcot, Oxon, UK.
authors.forename: A V
authors.initials: AV
authors.lastname: Patterson
authors.forename: N
authors.initials: N
authors.lastname: Robertson
authors.forename: S
authors.initials: S
authors.lastname: Houlbrook
authors.forename: M A
authors.initials: MA
authors.lastname: Stephens
authors.forename: G E
authors.initials: GE
authors.lastname: Adams
authors.forename: A L
authors.initials: AL
authors.lastname: Harris
authors.forename: I J
authors.initials: IJ
authors.lastname: Stratford
authors.forename: J
authors.initials: J
authors.lastname: Carmichael
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D006801:Humans; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000502:physiology*; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D013778:Tetrazolium Salts / Q000378:metabolism; D013844:Thiazoles / Q000378:metabolism; D000077704:Tirapazamine; D014227:Triazines / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects*
chemical_list: D000970:Antineoplastic Agents; D011838:Radiation-Sensitizing Agents; D013778:Tetrazolium Salts; D013844:Thiazoles; D014227:Triazines; D000077704:Tirapazamine; D016660:NAD(P)H Dehydrogenase (Quinone); C022616:thiazolyl blue