Induction of chromosome aberrations in unirradiated chromatin after partial irradiation of a cell nucleus

Purpose : It is generally accepted that chromosome exchanges in irradiated cells are formed through interactions between separate DNA double-strand breaks (DSB). Here we tested whether non-irradiated DNA participates in the formation of chromosome aberrations when complex DNA DSB are induced elsewhere in the nucleus. Materials and methods : Synchronized Chinese hamster cells containing an X chromosome with a late replicating q arm (X q domain) were labelled with 125 I-iododeoxyuridine (125 IdUrd) in a period of S-phase when the vast majority of the X q domain was not replicating. DNA damage from 125 I decay was accumulated at the G1/S border while the cells were stored in liquid nitrogen. Decay of 125 I induced DSB in the immediate vicinity of the 125 I atom. Chromosome aberrations involving what is essentially the 125 I-free X domain were scored at the first mitosis after cell thawing. As a positive control, cells were treated with 125 IdUrd at a later period in S-phase when the X q domain replicates, yielding a labelled X q domain. Results : The 125 I-free X q domain exhibited chromosome aberrations (exchanges and fragments). The frequency of these aberrations was linearly dependent on the number of 125 I decays elsewhere in the cell nucleus. The efficiency of formation of chromosome aberrations by the 125 I-free X q domain was approximately half of that observed in the 125 I-labelled X q domain. Conclusions : The involvement of the 125 I-free X q domain in chromosome aberrations suggests that DNA not damaged by the decay of incorporated 125 I can interact with damaged DNA, indicating the existence of an alternative pathway for the formation of chromosome aberrations.