Disparate effects of 5-bromodeoxyuridine on sister-chromatid exchanges and chromosomal aberrations in Bloom syndrome fibroblasts.
The existence of a high frequency of spontaneous sister-chromatid exchanges (SCEs) in Bloom syndrome (BS) has thus far been supported by data on a small number of BS cell lines. To examine the cause of baseline SCEs more broadly, the frequencies of SCEs, as well as chromosomal aberrations (CAs) in 4 additional BS fibroblast strains were compared, under different assay and cell culture conditions, with those of normal cells in the range of approximately 0.9-90% 5-bromodeoxyuridine (BrdUrd) substitution into template DNA. SCEs at low levels of BrdUrd substitution were detected by an extremely sensitive immunofluorescent technique. From approximately 0.9% to 4.5% BrdUrd substitution, the SCE frequency in BS cells remained constant, at a level (40/cell) 8 times higher than that of normal cells. As BrdUrd substitution increased further, the SCE frequency in BS cells increased almost linearly, reaching 70-100 per cell at approximately 90% substitution, while the SCE increment in control fibroblasts was less than 5 per cell. Analysis of SCEs in 3 successive replication cycles similarly revealed that the SCE increment in BS cells depended on BrdUrd only at a high BrdUrd substitution level. In contrast to data on SCEs, CA induction by incorporated BrdUrd in BS cells was only slightly higher than that in normal cells. Thus, BS cells are extremely sensitive to BrdUrd for SCE induction, but much less so for CA induction.
Tsuji
H
H
Genetics Division, Children's Hospital, Boston, MA.
Heartlein
M W
MW
Latt
S A
SA
D001816:Bloom Syndrome / Q000235:genetics / Q000473:pathology*; D001973:Bromodeoxyuridine / Q000494:pharmacology*; D002478:Cells, Cultured; D002869:Chromosome Aberrations; D003841:Deoxycytidine / Q000494:pharmacology; D005347:Fibroblasts / Q000187:drug effects* / Q000648:ultrastructure; D005467:Floxuridine / Q000494:pharmacology; D006801:Humans; D012854:Sister Chromatid Exchange / Q000187:drug effects*
D005467:Floxuridine; D003841:Deoxycytidine; D001973:Bromodeoxyuridine