Analysis of spontaneous sister-chromatid exchanges in vivo by three-way differentiation

By applying an adaptation of the method of three-way differentiation to murine bone marrow cells in vivo, the basal frequency of sister-chromatid exchange (SCE) per cell was evaluated. An SCE frequency directly proportional to the estimated relative incorporation of 5-bromodeoxyuridine (BrdU) to the chromosomes was observed for the 3 consecutive cell cycles, implying that the majority, if not all, of the SCEs in vivo were produced by the incorporated BrdU. This conclusion was supported by the finding that in the first cycle of division, a very high frequency of cells without SCE was observed. From these data, a spontaneous frequency of SCE as low as 0.15 SCE/cell/cell cycle was inferred.