Cytotoxic effects of the hypoxic cell radiosensitizer Ro 7-0582 to tumor cells in vivo.
Cytotoxic effects of the hypoxic cell radiosensitizer Ro 7-0582 to tumor cells in vivo.
复制标题
缺氧细胞放射增敏剂 Ro 7-0582 对体内肿瘤细胞的细胞毒性作用。
作者：
J. Brown
使用两种可移植肿瘤（BALB/c 小鼠的 EMT6 肿瘤和 C3H 小鼠的 MDAH/MCa4 肿瘤）体内研究了硝基咪唑 Ro 7-0582 对肿瘤细胞的细胞毒性。研究发现，高剂量的Ro 7-0582（1 mg/g）对大约90%的肿瘤细胞具有毒性，毒性仅发生在肿瘤含有缺氧细胞时，并且毒性针对缺氧和氧合良好的细胞。此外，与未受辐射的肿瘤细胞相比，受辐射的肿瘤细胞几乎没有或没有选择性毒性。在注射 1 mg/g Ro 7-0582 的 C3H 小鼠的 MDAH/MCa4 肿瘤的肿瘤治愈实验中，评估了细胞毒性和放射增敏作用的相对贡献。计算表明，在没有细胞毒性的情况下，仅由放射增敏引起的剂量修正因子将为 2.02，而不是观察到的值 2.30。在 0.3 mg/g 的较低剂量下未观察到毒性。
The cytotoxicity of the nitroimidazole Ro 7-0582 to tumor cells has been studied in vivo using two transplantable tumors, the EMT6 tumor in BALB/c mice and the MDAH/MCa4 tumor in C3H mice. It was found that a high dose of Ro 7-0582 (1 mg/g) was toxic to approximately 90% of the tumor cells, that the toxicity only occurred when the tumor contained hypoxic cells, and that the toxicity was directed at both hypoxic and well-oxygenated cells. Also, there was little or no selective toxicity to irradiated, as opposed to unirradiated, tumor cells. The relative contributions of cytotoxicity and radiosensitization were evaluated in a tumor cure experiment for the MDAH/MCa4 tumor in C3H mice injected with 1 mg/g of Ro 7-0582. Calculations showed that in the absence of cytotoxicity the dose modification factor due to radiosensitization alone would have been 2.02 rather than the value of 2.30 observed. No toxicity was observed at the lower dose of 0.3 mg/g.