Ohizumi Y, Shibata C, Maezawa H, Ushiro S, Mori T
Gan. 1981 Oct;72(5):717-22.
The cytotoxic and radiosensitizing effects of low concentrations of misonidazole were examined by measurement of the colony-forming ability and growth of HeLa S3 cells. Under hypoxic conditions, cytotoxicity depended on the misonidazole concentration and the exposure time. After 24 hr exposure, the surviving fraction of cells treated with 0.1 mM misonidazole decreased to 0.2. The ability of cells to adhere to the growth surface of plastic dishes was reduced by 0.1 mM misonidazole upon 24 hr hypoxia and this effect persisted even during subsequent euoxia, irrespective of whether the drug was removed from the original growth medium. The growth of aerobic cells was not affected when 0.1 mM misonidazole containing medium, obtained from the hypoxia-treated dishes, was applied, nor when those cells were exposed for 72 hr to freshly prepared 1.0 mM misonidazole. Upon 24 hr exposure, 0.1 mM misonidazole exerted no obvious radiosensitizing effect on hypoxic cells. Based on these results, it is suggested that continuous administration of low doses of misonidazole may be efficacious as a specific chemotherapeutic in the treatment of hypoxic cells in tumor tissue.
通过测量HeLa S3细胞的集落形成能力和生长情况，研究了低浓度米索硝唑的细胞毒性和放射增敏作用。在缺氧条件下，细胞毒性取决于米索硝唑的浓度和暴露时间。暴露24小时后，用0.1 mM米索硝唑处理的细胞存活分数降至0.2。在缺氧24小时后，0.1 mM米索硝唑可降低细胞粘附于塑料培养皿生长表面的能力，且即使在随后的常氧条件下，这种作用仍持续存在，无论药物是否从原始生长培养基中去除。当应用从缺氧处理的培养皿中获得的含0.1 mM米索硝唑的培养基时，需氧细胞的生长不受影响，当这些细胞暴露于新鲜制备的1.0 mM米索硝唑72小时时也不受影响。暴露24小时后，0.1 mM米索硝唑对缺氧细胞没有明显的放射增敏作用。基于这些结果，提示持续给予低剂量米索硝唑作为一种特异性化疗药物，可能对治疗肿瘤组织中的缺氧细胞有效。
