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Int J Radiat Oncol Biol Phys. 1994 May 15;29(2):369-72.

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

Author information

1
MRC Radiobiology Unit, Chilton, Didcot, Oxon, UK.

Abstract

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.

PMID:
8195035
DOI:
10.1016/0360-3016(94)90291-7
[Indexed for MEDLINE]

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