Presence of Abnormally High Incidences of Sister Chromatid Exchanges in Three Successive Cell Cycles in Bloom's Syndrome Lymphocytes

The frequencies of sister chromatid exchanges (SCEs) were examined in phytohaemagglutinin-stimulated blood lymphocytes of a normal individual, a Bloom's syndrome heterozygote (bl/+), and two Bloom's syndrome homozygotes (bl/bl). To determine the baseline SCE frequencies, lymphocytes were cultured with various concentrations of 5-bromodeoxyuridine (BrdUrd) for two cell cycles. The incidence of SCEs per two cell cycles in bl/bl lymphocytes levelled off at BrdUrd concentrations below 10 micrograms/ml while that in normal and bl/+ lymphocytes stayed constant below 7.5 micrograms/ml. The baseline SCE frequency in bl/bl cells was ten times higher than that in normal and bl/+ cells. At BrdUrd concentrations above 15 micrograms/ml, SCEs in bl/bl cells were induced more frequently than in normal and bl/+ cells. These results indicate that at low concentrations BrdUrd has a minimal effect on the induction of SCEs in all individuals, while at higher concentrations the BrdUrd incorporated in bl/bl cells has a larger effect than that in normal and bl/+ cells. To elucidate the effect of BrdUrd incorporated into the daughter and parental DNA strands on SCE induction, SCEs occurring during each cell cycle were examined separately in three-way or two-way differentially stained, third-cycle metaphases. The incidence of SCEs detected in each cell cycle at 5 micrograms/ml BrdUrd was constant in all individuals and the rates of SCEs in each cell cycle in bl/bl cells were remarkably higher than those observed in normal and bl/+ cells.(ABSTRACT TRUNCATED AT 250 WORDS)