The effect of hypoxia on the growth and radiation response of mammalian cells in culture

During prolonged hypoxia, a progressive change occurs in the radiosensitivity of cultured mammalian cells. An attempt was made to determine whether this could be explained on the basis of a progressive change in the life cycle or age distribution of cells during hypoxia. Cell population growth kinetics and the cell life cycle were studied by two conventional methods of analysis. Both indicated an appreciable heterogeneity in the cell populations with regard to the ability of individual cells to negotiate their life cycle during hypoxia. This heterogeneity was confirmed by studying the development of individual microcolonies under hypoxia. From this study, the following conclusions were reached regarding changes which occurred during hypoxia: (1) the growth rate was decreased and the life cycle lengthened; (2) the overall proportion of cells in DNA synthesis decreased with time; (3) on average, a disproportionate lengthening of the G1 phase of the life cycle was implicated; and (4) these changes were accompanied by a decrease in the shoulder and an increase in the D0 for the cell survival curve following irradiation with 60Co γ rays. Changes in the radiation response for reasons other than changes in the life cycle or age distribution could not be ruled out.