Pettersen E O, Lindmo T
Br J Cancer. 1981 Mar;43(3):355-66. doi: 10.1038/bjc.1981.56.
Populations of NHIK 3025 cells synchronized by mitotic selection were exposed at 37 degrees C to extreme hypoxia in absence and presence of misonidazole (MISO). Cells in G1, S or G2 and mitosis were treated for 3 h. Inhibition of cell-cycle progression by this treatment was measured by flow cytometry of DNA histograms and cell inactivation was measured by colony formation. The exposure to hypoxia alone of cells in G1 or in G2 and mitosis led to only minor cell-cycle inhibition, and hardly reduced cell survival. However, the exposure of cells in S to hypoxia alone had a strong inhibitory effect on cell-cycle progression, and cell survival was only 40% of untreated cells. Low concentrations of MISO (0.05-0.4 mM) during exposure of cells in S to hypoxia, produced less cell-cycle inhibition than after hypoxia alone, and cell survival was restored to 100%. The presence of MISO during the 3h exposure to hypoxia of cells in G1 or in G2 and mitosis only increased the effects of hypoxia alone. MISO at concentrations greater than 0.8 mM during hypoxia produced cell inactivation, for all phases of the cell cycle, comparable to that already known from the literature.
通过有丝分裂选择同步化的NHIK 3025细胞群体，在37℃下于不存在和存在米索硝唑（MISO）的情况下暴露于极端低氧环境。处于G1、S或G2期以及有丝分裂期的细胞接受3小时处理。通过DNA直方图的流式细胞术测量这种处理对细胞周期进程的抑制作用，并通过集落形成测量细胞失活情况。仅将处于G1期或G2期以及有丝分裂期的细胞暴露于低氧环境，仅导致轻微的细胞周期抑制，并且几乎不降低细胞存活率。然而，仅将处于S期的细胞暴露于低氧环境对细胞周期进程具有强烈的抑制作用，并且细胞存活率仅为未处理细胞的40%。在将处于S期的细胞暴露于低氧环境期间，低浓度的MISO（0.05 - 0.4 mM）产生的细胞周期抑制作用比仅低氧处理后更小，并且细胞存活率恢复到100%。在将处于G1期或G2期以及有丝分裂期的细胞暴露于低氧环境的3小时期间，MISO的存在仅增强了低氧单独作用的效果。在低氧期间，浓度大于0.8 mM的MISO对细胞周期的所有阶段均产生细胞失活作用，这与文献中已知的情况相当。
