Varghese A J, Gulyas S, Mohindra J K
Cancer Res. 1976 Oct;36(10):3761-5.
Incubation of Chinese hamster ovary cells and KHT murine fibrosarcoma tumor cells in the absence of oxygen with 1-[2-14C]nitro-1-imidazolyl)-3-methoxy-2-propanol, one of the most effective radiation sensitizers of hypoxic cells, results in the preferential reduction of 1-[2-14C]nitro-1-imidazolyl)-3-methoxy-2-propanol. The radioactivity associated with the acid-insoluble precipitate from cells incubated in nitrogen is about four times higher than that of cells incubated in air. When aqueous extracts of tissues of a C3H mouse bearing the KHT tumor, after i.p. injection with 1-[2-14C]nitro-1-imidazolyl)-3-methoxy-2-propanol, are analyzed, a reduction product is found in relatively higher yields in the tumor than in normal tissues. The relative radioactivity in the pellet from the tumor homogenate is also high in comparison with those of most normal tissues. These results provide suggestive evidence for a higher degree of hypoxic in the tumor than in most normal tissues. The formation of reduction products and their subsequent binding to macromolecules may explain the preferential toxicity of nitro compounds to mammalian cells under hypoxia conditions. These results suggest that some nitro compounds may be useful for the treatment of tumors having a high fraction of hypoxic cells even in the absence of radiation.
在无氧条件下，将中国仓鼠卵巢细胞和KHT小鼠纤维肉瘤肿瘤细胞与1-[2-¹⁴C]硝基-1-咪唑基)-3-甲氧基-2-丙醇（缺氧细胞最有效的放射增敏剂之一）一起培养，会导致1-[2-¹⁴C]硝基-1-咪唑基)-3-甲氧基-2-丙醇优先被还原。与在氮气中培养的细胞的酸不溶性沉淀物相关的放射性比在空气中培养的细胞高约四倍。当对经腹腔注射1-[2-¹⁴C]硝基-1-咪唑基)-3-甲氧基-2-丙醇的携带KHT肿瘤的C3H小鼠的组织水提取物进行分析时，发现肿瘤中还原产物的产率相对高于正常组织。与大多数正常组织相比，肿瘤匀浆沉淀物中的相对放射性也很高。这些结果提供了提示性证据，表明肿瘤中的缺氧程度高于大多数正常组织。还原产物的形成及其随后与大分子的结合可能解释了硝基化合物在缺氧条件下对哺乳动物细胞的优先毒性。这些结果表明，即使在没有辐射的情况下，一些硝基化合物可能对治疗具有高比例缺氧细胞的肿瘤有用。
