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)
D001816:Bloom Syndrome / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D001973:Bromodeoxyuridine / Q000494:pharmacology; D002453:Cell Cycle; D002869:Chromosome Aberrations; D006801:Humans; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000166:cytology* / Q000276:immunology; D012854:Sister Chromatid Exchange / Q000187:drug effects
D001973:Bromodeoxyuridine