Are single or multiple mechanisms involved in radiation-induced mammalian cell killing?

The survival curve of repair-competent mammalian cells exposed to X- or to gamma-rays has a shoulder usually followed by a region of exponential survival. A curve of this shape results from the accumulation of subeffective damage in the shoulder region. This damage has been called sublethal [Elkind & Sutton (1959), Nature, 184, 1293], a designation the basis for which has been questioned by Alper [(1977), Brit. J. Radiol., 50, 459] who noted that if the shoulder results from the progressive reduction of a repair capacity, then the damage would be potentially lethal. A series of experiments is analyzed to show that requiring an equivalence between sublethal and potentially lethal damage has limited usefulness because as many questions are raised as are answered. Moreover, the sector of repair corresponding to the shoulder region is small compared to the sector of damage which must be repaired if only a minority of the lesions in DNA are effective. It is concluded that multiple mechanism may be involved in cell killing and, in addition, that the processes connected with the shoulder region of the survival curve amount to only the tip of an iceberg whose size and properties are yet to be fully appreciated.