Studies with bleomycin and misonidazole on aerated and hypoxic cells.
Studies with bleomycin and misonidazole on aerated and hypoxic cells.
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DOI：
10.1038/bjc.1978.34
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发表时间：
1978-02
影响因子：
8.8
通讯作者：
Hall, E J
中科院分区：
文献类型：
--
作者：
Roizin-Towle, L;Hall, E J
博来霉素是一种化疗药物，主要用于治疗鳞状细胞癌，而米索硝唑是一种有效的放射增敏剂和有效的细胞毒剂，选择性地影响缺氧细胞。使用 V79 中国仓鼠细胞研究博莱霉素 (BLM) 在通气和缺氧条件下的细胞毒性与药物浓度的函数关系。在 17.5 摄氏度的低温或 42.5 摄氏度的高温下，缺氧细胞比曝气细胞对 BLM 的杀伤更敏感。在这两个温度中的任何一个温度下，细胞周期的进展都会受到抑制。然而，在 37.5 摄氏度（模拟临床情况）时，敏感性会逆转，缺氧细胞的抵抗力明显增强。尽管涉及许多因素，但主要原因是充气细胞正在循环，而缺氧细胞则不然。通气细胞可以进入细胞周期的各个阶段，在该阶段它们对 BLM 的杀伤更加敏感。米索硝唑 (=Ro-07-0582) 与 BLM 联合使用，因为其作用方式已被证明对于杀死缺氧细胞具有特异性。当面对实体瘤的缺氧细胞成分时，它与 BLM 联合使用可能在化疗中具有潜在用途。
Bleomycin is a chemotherapuetic drug used primarily in the treatment of squamous-cell carcinoma, while misonidazole is an effective radiosensitizer and potent cytotoxic agent selectively affecting hypoxic cells. V79 Chinese hamster cells were used to investigate the cytotoxicity of bleomycin (BLM) under aerated and hypoxic conditions as a function of drug concentration. At a lowered temperature of 17.5 degrees C, or at an elevated temperature of 42.5 degrees C, hypoxic cells are more sensitive to killing by BLM than aerated cells. At either of these temperatures, progression through the cell cycle is inhibited. However, at 37.5 degrees C, mimicking a clinical situation, the sensitivies are reversed, and hypoxic cells are appreciably more resistant. Although many factors are involved, the major reason for this is that aerated cells are cycling while hypoxic cells are not. Aerated cells can progress into phases of the cell cycle where they are more sensitive to killing by BLM. Misoinidazole (=Ro-07-0582) was used in combination with BLM, since its mode of action has been shown to be psecific for killing hypoxic cells. It concomitant use with BLM could be of potential use in chemotherapy when confronted with the hypoxic cell component of solid tumours.