Synergism between halothane and nitrous oxide in the production of nuclear abnormalities in the dividing fibroblast

When Chinese hamster fibroblasts divide in the presence of halothane there is an increased incidence of cells with abnormal nuclei, both in mitosis and in interphase. The authors compared the effects of halothane and nitrous oxide separately and in combination. Nitrous oxide, 75 percent, alone had no significant effect compared with controls, less than 1.4 per cent of cells showing abnormalities, while halothane alone had a dose-dependent effect on both phases of the cell cycle. Halothane, 1 per cent, caused abnormalities in 7 per cent (SEM +/- 0.32) of cells in interphase and in 12 per cent (SEM +/- 0.95) of cells in mitosis, but the combination of 0.75 per cent halothane with 75 percent nitrous oxide produced 15 per cent (SEM +/- 0.68) abnormal cells in interphase and 22 per cent (SEM +/- 0.51) abnormal mitoses. Similar highly significant differences were obtained throughout the dose-response curves to as much as 4 per cent halothane in air and 2.35 per cent halothane in 75 per cent nitrous oxide. This appears to demonstrate synergism between halothane and nitrous oxide in the production of this particular side effect. In contrast, the effects of halothane and nitrous oxide on growth rate were additive.