Low concentrations of misonidazole counteract effects of extreme hypoxia on cells in S

Abstract

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.