EFFECTS OF MITOMYCIN-C AND PORFIROMYCIN ON EXPONENTIALLY GROWING AND PLATEAU-PHASE CULTURES
EFFECTS OF MITOMYCIN-C AND PORFIROMYCIN ON EXPONENTIALLY GROWING AND PLATEAU-PHASE CULTURES
复制标题
DOI：
10.1111/j.1365-2184.1994.tb01413.x
复制
发表时间：
1994-03-01
影响因子：
8.5
通讯作者：
HUGHES, CS
中科院分区：
文献类型：
--
作者：
ROCKWELL, S;HUGHES, CS
实验室研究和临床试验正在探索使用低氧导向的细胞毒性药物作为放射治疗的替代品。由于实体瘤中缺氧和与缺氧相关的微环境不足抑制细胞增殖，因此在癌症治疗中成功使用缺氧导向药物的基本要求是这些药物对静止肿瘤细胞以及通过细胞周期快速进展的肿瘤细胞具有毒性。本文报告的实验比较了丝裂霉素C和泊非霉素对EMT 6小鼠乳腺肿瘤细胞的指数生长和平台期培养物的细胞毒性。增殖状态的文化没有影响丝裂霉素C的细胞毒性在有氧或缺氧条件下，或在空气中的porfiromycin的细胞毒性。指数生长的培养物在缺氧条件下对泊非霉素的敏感性略高于平台期培养物，但增殖期和静止期细胞的敏感性之间的差异远小于需氧细胞和缺氧细胞之间的差异。在空气中或缺氧条件下，未发现Porfiromycin治疗后潜在致死性损伤修复的证据;这与丝裂霉素C的既往研究结果一致。因此，丝裂霉素C和扑非霉素表现出有效用作治疗实体瘤的低氧导向药物所需的对静止细胞的毒性。
Laboratory studies and clinical trials are exploring the use of hypoxia-directed cytotoxic agents as adjuncts to radiotherapy. Because hypoxia and the microenvironmental inadequacies associated with hypoxia in solid tumours inhibit cell proliferation, an essential requirement for the successful use of hypoxia-directed drugs in cancer therapy is that these drugs be toxic to quiescent tumour cells, as well as tumour cells progressing rapidly through the cell cycle. The experiments reported here compared the cytotoxicities of mitomycin C and porfiromycin to exponentially growing and plateau phase cultures of EMT6 mouse mammary tumour cells. The proliferative status of the cultures did not influence the cytotoxicity of mitomycin C under either aerobic or hypoxic conditions, or the cytotoxicity of porfiromycin in air. Exponentially growing cultures were slightly more sensitive than plateau phase cultures to porfiromycin in hypoxia, but the difference between the sensitivities of proliferating and quiescent cells was much smaller than the difference between aerobic and hypoxic cells. No evidence for repair of potentially lethal damage was found after treatment with porfiromycin in air or in hypoxia; this is in agreement with previous findings for mitomycin C. Mitomycin C and porfiromycin therefore exhibit the toxicity to quiescent cells needed for effective use as hypoxia-directed drugs for the treatment of solid tumours.