title: Chromosomal instability in B-lymphoblasotoid cell lines from Werner and Bloom syndrome patients.
abstract: Werner's syndrome (WS) and Bloom's syndrome (BS) are rare autosomal genetic diseases that predispose to cancer and are associated with genomic instability. To characterize the genomic instability of WS and BS, we analyzed and compared the cytogenetics of B-lymphoblastoid cell lines (LCLs) from WS and BS patients and healthy donors. Although, similar spontaneous frequencies of micronuclei (MN) and sister chromatid exchanges (SCE) were observed in LCLs from WS patients and healthy donors, they were much higher in BS-LCLs. We also examined the cells' cytotoxic and cytogenetic formation (MN) response to camptothecin (CAM), etoposide (ETO), 4-nitroquinoline 1-oxide (4NQO), and mitomycin C (MMC). Compared to healthy donor LCLs, BS-LCLs but not WS-LCLs tended to be resistant to cytotoxicity and sensitive to MN induction by 4NQO and MMC. Spectrum karyotyping analysis revealed that most WS- and BS-LCLs generated "variegated translocation mosaicism" at high frequencies during cell culture. These findings support the idea that the basis of genomic instability in WS is different from that in BS.
authors.affiliation: Division of Genetics and Mutagenesis, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, 158-8501, Tokyo, Japan. honma@nihs.go.jp
authors.forename: Masamitsu
authors.initials: M
authors.lastname: Honma
authors.forename: Satoshi
authors.initials: S
authors.lastname: Tadokoro
authors.forename: Hiroko
authors.initials: H
authors.lastname: Sakamoto
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Tanabe
authors.forename: Masanobu
authors.initials: M
authors.lastname: Sugimoto
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Furuichi
authors.forename: Takatomo
authors.initials: T
authors.lastname: Satoh
authors.forename: Toshio
authors.initials: T
authors.lastname: Sofuni
authors.forename: Makoto
authors.initials: M
authors.lastname: Goto
authors.forename: Makoto
authors.initials: M
authors.lastname: Hayashi
mesh_terms: D015112:4-Nitroquinoline-1-oxide / Q000494:pharmacology; D001402:B-Lymphocytes / Q000473:pathology*; D001816:Bloom Syndrome / Q000235:genetics*; D002166:Camptothecin / Q000494:pharmacology; D002273:Carcinogens / Q000494:pharmacology; D016022:Case-Control Studies; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002869:Chromosome Aberrations; D005047:Etoposide / Q000494:pharmacology; D004854:Herpesvirus 4, Human; D006801:Humans; D007621:Karyotyping; D008677:Metaphase; D048629:Micronuclei, Chromosome-Defective; D016685:Mitomycin / Q000494:pharmacology; D012854:Sister Chromatid Exchange / Q000187:drug effects; D014898:Werner Syndrome / Q000235:genetics*
chemical_list: D002273:Carcinogens; D016685:Mitomycin; D015112:4-Nitroquinoline-1-oxide; D005047:Etoposide; D002166:Camptothecin