Lin P S, Ho K C, Yang S J
Department of Radiation Oncology, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298, USA.
Cancer Lett. 1996 Aug 2;105(2):249-55. doi: 10.1016/0304-3835(96)04292-9.
Tirapazamine (Tira), a bioreductive agent, is highly toxic to cells under low oxygen conditions. Since active investigations of this agent are focusing on its potential as an adjunct of radiotherapy to improve overall effects on radioresistant hypoxic tumor cells, understanding its toxic mechanisms under aerobic conditions is important to the clinical application of this agent. Tira-treated V79 Chinese hamster cells were tested for cytotoxicity by colony assay and growth inhibition by the MTT assay. The survival of V79 cells after being exposed to 100 microM of Tira for 2 h was about 78% of untreated controls. The mitotic cell counts of V79 cells approached zero after 4 h treatment of Tira at 100 microM or 3 h at 300 microM. The fragmentation pattern of DNA isolated from cells 2 h after 300 microM Tira treatment showed characteristics of apoptotic cells. The induction of apoptosis by Tira was also detected by flow cytometric analysis and microscopic observation. These effects of Tira may be part of underlying toxic mechanisms to cells (including normal cells) under aerobic conditions.
替拉扎明（Tira）是一种生物还原剂，在低氧条件下对细胞具有高度毒性。由于对该药物的积极研究主要集中在其作为放射治疗辅助剂以提高对放射抗拒的缺氧肿瘤细胞的总体疗效，了解其在有氧条件下的毒性机制对于该药物的临床应用至关重要。通过集落测定法检测替拉扎明处理的V79中国仓鼠细胞的细胞毒性，并通过MTT测定法检测其生长抑制情况。V79细胞在暴露于100微摩尔替拉扎明2小时后的存活率约为未处理对照组的78%。在100微摩尔替拉扎明处理4小时或300微摩尔处理3小时后，V79细胞的有丝分裂细胞计数接近零。在300微摩尔替拉扎明处理2小时后从细胞中分离的DNA片段化模式显示出凋亡细胞的特征。通过流式细胞术分析和显微镜观察也检测到替拉扎明诱导的细胞凋亡。替拉扎明的这些作用可能是其在有氧条件下对细胞（包括正常细胞）潜在毒性机制的一部分。
