Radiosensitizing and Toxic Effects of the 2-Nitroimidazole Ro-07-0582 in Different Phases of the Cell Cycle of Extremely Hypoxic Human Cells in Vitro

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Abstract
The radiosensitizing effect of 5 and 30 mM of Ro-07-0582 (misonidazole) was studied at different stages of the cell cycle of mitotically selected human uterine carcinoma NHIK 3025 cells under aerobic and extremely hypoxic conditions. For cells irradiated under aerobic conditions no sensitizing effect was seen at any stage of the cell cycle. For cells irradiated under extremely hypoxic conditions there was a lower sensitizing effect in mid-G1 [1st gap phase] than in mid-S [synthetic phase] for low radiation doses (in the initial region of the dose-response curves). For high radiation doses no significant difference in sensitizing effect on cells in mid-G1 and mid-S was seen. For cells in mid-G1 the sensitizing effect increased with increasing radiation dose. The toxic effect of 30 mM Ro-07-0582, as measured by loss of reproductive capacity, was studied at room temperature for contact times up to 6 h under aerobic conditions and 3 h under extremely hypoxic conditions. While no effect was seen under aerobic conditions, there was a toxic effect for contact intervals above 1 h under extremely hypoxic conditions. Cells in S were more sensitive to the toxic effect of Ro-07-0582 than cells in G1. Implications for clinical use are discussed.