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首页> 外文期刊>Mutation research. Genetic toxicology testing >ASSESSMENT OF MICRONUCLEUS INDUCTION IN SCCVII CELLS TREATED WITH BIOREDUCTIVE AGENTS, WIN 59075 (SR 4233) AND MITOMYCIN C, UNDER AEROBIC AND HYPOXIC CONDITIONS
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ASSESSMENT OF MICRONUCLEUS INDUCTION IN SCCVII CELLS TREATED WITH BIOREDUCTIVE AGENTS, WIN 59075 (SR 4233) AND MITOMYCIN C, UNDER AEROBIC AND HYPOXIC CONDITIONS

机译：在有氧和低氧条件下，用生物还原剂，WIN 59075（SR 4233）和丝裂霉素C处理的SCCVII细胞中的微核诱导评估

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WIN 59075 (SR4233, tirapazamine) is a promising bioreductive antitumor agent preferentially more toxic to hypoxic cells and presently undergoing phase I clinical trials. In this investigation, we have examined the applicability of the cytokinesis-block micronucleus assay to assess the effects of bioreductive agents. SCCVII tumor cells were treated with WIN 59075 or mitomycin C at various concentrations under aerobic and hypoxic conditions. Significant induction of micronuclei in binucleate cells was demonstrated in a dose-dependent fashion and it appeared to be strongly correlated with the loss of clonogenicity in the colony assay. Both agents showed selectively higher toxicity to hypoxic cells than to aerobic cells and the ratios of the concentrations required to obtain the equivalent effects under aerobic and hypoxic conditions could be also estimated by this method as follows: the hypoxic toxicity ratios were 120-130 for WIN 59075 and 3.0-3.3 for mitomycin C. For several favorable characteristics, the cytokinesis-block micronucleus assay can provide an alternative, rapid, and reproducible means for evaluation of antitumor activities from chromosomal breakage caused by the bioreductive agents.
机译：WIN 59075（SR4233，替拉帕明）是一种有前途的生物还原抗肿瘤剂，对低氧细胞的毒性更高，目前正在进行I期临床试验。在这项调查中，我们已经检查了胞质分裂阻滞微核试验评估生物还原剂效果的适用性。在有氧和低氧条件下，以不同浓度的WIN 59075或丝裂霉素C处理SCCVII肿瘤细胞。以剂量依赖的方式证明了双核细胞中微核的显着诱导，并且似乎与菌落测定中克隆形成力的丧失密切相关。两种药物对缺氧细胞的选择性毒性都高于对需氧细胞的毒性，通过该方法还可估算出在需氧和缺氧条件下获得等效作用所需的浓度比：WIN的低氧毒性比为120-130对于丝裂霉素C，为59075和3.0-3.3。为了获得几个有利的特征，胞质分裂阻滞微核试验可提供一种替代，快速且可重现的方法，用于评估由生物还原剂引起的染色体断裂引起的抗肿瘤活性。

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