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 IC 50 range from 10.2–120 μM and from 155–1230 for 96 and 3 h aerobic exposures, respectively. In N 2, IC 50S ranged from 8–55 μM. 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.
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