Cytotoxic effect of misonidazole and cyclophosphamide on aerobic and hypoxic cells in a C3H mammary carcinoma in vivo.
Cytotoxic effect of misonidazole and cyclophosphamide on aerobic and hypoxic cells in a C3H mammary carcinoma in vivo.
复制标题
Misonidazole和环磷酰胺对体内C3H乳腺癌中有氧细胞和低氧细胞的细胞毒性作用。
DOI：
10.1038/bjc.1990.13
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发表时间：
1990-01
影响因子：
8.8
通讯作者：
Overgaard J
中科院分区：
文献类型：
--
作者：
Grau C;Bentzen SM;Overgaard J
本文研究了硝基芳香类放射增敏剂米索硝唑（MISO）对烷化剂环磷酰胺（CTX）的化疗增敏作用。使用局部肿瘤对照（TCD 50）测定间接测量对需氧和缺氧细胞的选择性细胞毒性。根据在空气中或在夹紧条件下照射的肿瘤的TCD 50 S之间的剂量差异计算缺氧分数。药物治疗后肿瘤细胞的相对存活率表示为存活分数（SF）。CTX（100毫克kg-1）被发现是相当多的毒性对缺氧比有氧细胞（SF 4%对52%）。MISO（1000 mg kg-1）几乎只对缺氧细胞有毒性（SF 22%）。当MISO和CTX同时给药时，观察到存活分数降低。发现对充气细胞的影响比添加毒性的预期高10倍，表明MISO与CTX联合使用时对这些细胞具有化学增敏作用。没有发现协同效应对放射生物学缺氧细胞。缺氧对化疗增敏作用的确切作用似乎是复杂的，需要在未来进行更多的研究。
The chemosensitising effect of the nitroaromatic radiosensitiser misonidazole (MISO) on the alkylating agent cyclophosphamide (CTX) has been investigated in a C3H mammary carcinoma in CDF1 mice. The selective cytotoxicity against aerobic and hypoxic cells was measured indirectly, using a local tumour control (TCD50) assay. The hypoxic fraction was calculated from the dose difference between the TCD50S for tumours irradiated either in air or under clamped conditions. The relative survival of tumour cells after drug therapy was expressed as a surviving fraction (SF). CTX (100 mg kg-1) was found to be considerably more toxic towards hypoxic than aerobic cells (SF 4% versus 52%). MISO (1000 mg kg-1) was almost exclusively toxic to hypoxic cells (SF 22%). When MISO and CTX were administered simultaneously a decrease in the surviving fraction was observed. The effect on aerated cells was found to be 10-fold more than expected from addition of toxicities, suggesting a chemosensitising effect on these cells by MISO when used in combination with CTX. No synergistic effect was found on radiobiologically hypoxic cells. The exact role of hypoxia for the development of chemosensitisation seems to be complex and requires additional research in the future.