Study will be undertaken of the modifications of responses of cultured mammalian cells to X-irradiation, brought about by treatment with different agents that affect the expression of potentially lethal damage, i.e., damage whose expression can be modified by appropriate treatment of the cell. In general, synchronous populations of established cell lines will be used. Cell viability will be measured by colony-forming ability as a function of X-ray dose, time, concentration, and cell age in the generation cycle both at the time of treatment and the time of response. Particular emphasis will be directed toward the impact of the various treatments on the characteristics of the dose-survival and the age-survival functions. The data should (1) facilitate assessment of the role of repair processes in the cellular radiation syndrome, particularly in the observed dependence of cell survival on X-ray dose and on cell age, and in the cell-line-specific responses to X-irradiation; and (2) provide insight into the nature of the lethal cellular lesions and the relation of those lesions to lesions that are potentially lethal.
