Patterson A V, Robertson N, Houlbrook S, Stephens M A, Adams G E, Harris A L, Stratford I J, Carmichael J
MRC Radiobiology Unit, Chilton, Didcot, Oxon, UK.
Int J Radiat Oncol Biol Phys. 1994 May 15;29(2):369-72. doi: 10.1016/0360-3016(94)90291-7.
To determine the dependency of the aerobic and hypoxic toxicity of tirapazamine on the intracellular activity of DT-diaphorase.
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.
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).
The expression of DT-diaphorase in human tumor cells does not affect the toxicity of tirapazamine.
确定替拉扎明的需氧和缺氧毒性对DT-黄递酶细胞内活性的依赖性。
使用了一组18种人类细胞系，主要包括小细胞和非小细胞肺癌及乳腺癌细胞系。在细胞裂解物的胞质制剂中测定DT-黄递酶的活性。在需氧暴露96小时或3小时或缺氧处理3小时后，使用MTT法测定替拉扎明的毒性。
这些细胞系的DT-黄递酶活性范围为5000倍。在毒性实验中，96小时和3小时需氧暴露的IC50值分别为10.2 - 120微摩尔和155 - 1230微摩尔。在氮气环境中，IC50值范围为8 - 55微摩尔。没有一个毒性值与DT-黄递酶的活性相关，需氧：缺氧毒性比值（差异毒性）也不相关。
人类肿瘤细胞中DT-黄递酶的表达不影响替拉扎明的毒性。
