title: Asynchronous Replication in Lymphocytes from Patients with Inflammatory Bowel Disease and Primary Sclerosing Cholangitis.
abstract: Primary sclerosing cholangitis (PSC) and inflammatory bowel disease (IBD) are associated chronic inflammatory diseases with malignant potential. Loss of replication synchrony during the S-phase of the cell cycle has been shown to be linked to several malignant and premalignant states. This study evaluated temporal differences in replication timing between these diseases. The replication pattern of peripheral blood lymphocytes obtained from patients with PSC and IBD and healthy individuals was analyzed by fluorescence in situ hybridization (FISH) in 2 pairs of alleles, in 15qter and 13qter. Asynchrony was determined by the presence of 1 single and 1 set of double dots in the same cell. Samples from subjects with PSC showed significantly greater temporal differences in replication timing, in contrast to the high level of synchrony observed in samples from healthy individuals (p = 0.045). Samples from IBD patients exhibited a nonsignificant increase in replication asynchrony. We believe that these results reflect impairment in the replication control of structural homologous loci in PSC, and that this phenomenon may be correlated with the inflammation-induced malignant potential of this condition.
authors.affiliation: Institute of Gastroenterology and Hepatology, Meir Medical Center, Kfar Saba, Israel.
authors.forename: Ido
authors.initials: I
authors.lastname: Laish
authors.forename: Tal
authors.initials: T
authors.lastname: Biron-Shental
authors.forename: Hila
authors.initials: H
authors.lastname: Katz
authors.forename: Meytal
authors.initials: M
authors.lastname: Liberman
authors.forename: Yona
authors.initials: Y
authors.lastname: Kitay-Cohen
authors.forename: Fred Meir
authors.initials: FM
authors.lastname: Konikoff
authors.forename: Aliza
authors.initials: A
authors.lastname: Amiel
mesh_terms: D002455:Cell Division / Q000235:genetics; D049109:Cell Proliferation; D002478:Cells, Cultured; D015209:Cholangitis, Sclerosing / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000453:epidemiology; D004261:DNA Replication; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D015212:Inflammatory Bowel Diseases / Q000235:genetics*; D008214:Lymphocytes / Q000473:pathology*; D008297:Male; D008875:Middle Aged