Modulation of survival and transformation during plateau-phase holding of UV-irradiated mouse cells.

It has been known that in bacteria, DNA adducts induced by ultraviolet light are repaired via multiple pathways (Clark and Volkert, 1978; Smith, 1978). In all likelihood, the same sort of multiplicity of repair pathways exists in mammalian cells since distinctly different repair defects in human genetic disorders have all given rise to UV sensitivity (Friedberg et al., 1979; Arlett and Lehmann, 1978). Whether a given repair pathway can function depends on such factors as the cellular physiological state and cell-cycle parameters. For example, UV-induced pyrimidine dimers are subject to excision repair when they are located on DNA segments not being replicated. A whole other set of processes would have to be invoked to deal with the same adducts if they are encountered by the replication fork (Cleaver, 1978). The nature of these latter processes are as yet poorly defined. In order to assess exclusively the biological consequences of repair activities which are not related to DNA replication, we have used cultured mouse fibroblasts in the quiescent plateau phase of growth. By holding the cells in plateau phase for various durations of time after UV irradiation, thereby allowing such repair processes to be carried out to various extents before DNA replication is initiated, the biological effects of these repair processes have been measured with respect to the end points of clonogenic survival and malignant transformation.