http://http://dspace.unitus.it:80 The DSpace digital repository system captures, stores, indexes, preserves, and distributes digital research material. Wed, 19 Jun 2013 04:34:41 GMT 2013-06-19T04:34:41Z http://hdl.handle.net/2067/1716 Title: Werner’s sindrome lymphoblastoid cells are hypersensitive to topoisomerase II inhibitors in the G2 phase of the cell cycle Authors: Pichierri, Pietro; Franchitto, Annapaola; Mosesso, Pasquale; Proietti De Santis, Luca; Balajee, Adayabalam S.; Palitti, Fabrizio Abstract: Werner's syndrome (WS) is a rare autosomal recessive human disorder and the patients exhibit many symptoms of accelerated ageing in their early adulthood. The gene (WRN) responsible for WS has been biochemically characterised as a 3'-5' helicase and is homologous to a number of RecQ superfamily of helicases. The yeast SGS1 helicase is considered as a human WRN homologue and SGS1 physically interacts with topoisomerases II and III. In view of this, it has been hypothesised that the WRN gene may also interact with topoisomerases II and III. The purpose of this study is to determine whether the loss of function of WRN protein alters the sensitivity of WS cells to agents that block the action of topoisomerase II. This study deals with the comparison of the chromosomal damage induced by the two anti-topoisomerase II drugs, VP-16 and amsacrine, in both G1 and G2 phases of the cell cycle, in lymphoblastoid cells from WS patients and from a healthy donor. Our results show that the WS cell lines are hypersensitive to chromosome damage induced by VP-16 and amsacrine only in the G2 phase of the cell cycle. No difference either in the yield of the induced aberrations or SCEs was found after treatment of cells at G1 stage. These data might suggest that in WS cells, because of the mutation of the WRN protein, the inhibition of topoisomerase II activity results in a higher rate of misrepair, probably due to some compromised G2 phase processes involving the WRN protein. Description: L'articolo é disponibile sul sito dell'editore: http://www.sciencedirect.com Fri, 31 Dec 1999 23:00:00 GMT http://hdl.handle.net/2067/1716 1999-12-31T23:00:00Z http://hdl.handle.net/2067/1720 Title: Chromosome radiosensitivity in human G2 lymphocytes and cell cycle progression Authors: Palitti, Fabrizio; Pichierri, Pietro; Franchitto, Annapaola; Proietti De Santis, Luca; Mosesso, Pasquale Abstract: PURPOSE: To investigate the possibility that the differential G2-phase radiosensitivity of human peripheral blood lymphocytes, found in normal individuals using the 'G2-phase chromosome radiosensitivity assay', could be attributed to heterogeneity in cellular progression to mitosis rather than differences in radiosensitivity. MATERIALS AND METHODS: Human peripheral blood lymphocytes, from four different donors, were exposed to 50 cGy X-rays and sampled at different times. The progression of cells into mitosis was monitored by 5-bromo 2'-deoxyuridine (BrdUrd) incorporation. RESULTS: The heterogeneous G2-phase chromosome radiosensitivity among different donors was abolished when homogeneous G2-phase cell populations were scored; they contained similar frequencies of cells in early or late G2-phase. CONCLUSIONS: The heterogeneous G2-phase chromosome radiosensitivity, usually found in different normal donors, is caused by the analysis of different cell populations rather than reflecting intrinsic differences in radiosensitivity Description: L'articolo è disponibile sul sito dell'editore: http://informahealthcare.com Thu, 31 Dec 1998 23:00:00 GMT http://hdl.handle.net/2067/1720 1998-12-31T23:00:00Z http://hdl.handle.net/2067/1717 Title: Lack of effect of caffeine post-treatment on X-rays chromosomal aberrations in Werner's syndrome lymphoblastoid cell lines: A Preliminary Report Authors: Franchitto, Annapaola; Proietti De Santis, Luca; Pichierri, Pietro Abstract: PURPOSE: To investigate whether in Werner's syndrome cells the G2 phase of the cell cycle has some abnormal response to post-treatment with agents such as caffeine and hydroxyurea known to interfere with cellular response to DNA damage. MATERIALS AND METHODS: Two Werner's syndrome lymphoblastoid cell lines (KO375 and DJG) and the normal cell line SNW646 were exposed to 50 cGy of X-rays or mitomycin-C and posttreated with caffeine or hydroxyurea in the G2 phase of the cell cycle. RESULTS: Hydroxyurea post-treatment potentiated the X-ray-induced aberration levels both in the normal and Werner's syndrome (KO375 and DJG) cell lines; in contrast caffeine was only effective in the normal cell line. Similar results were observed when Werner's syndrome cells were treated in the G1 phase with the S-dependent agent mitomycin-C and post-treated with caffeine in G2, extending the observation that Werner's syndrome cells are unaffected by caffeine G2 post-treatment. CONCLUSIONS: These results show a lack of caffeine effect in Werner's syndrome cells, suggesting an involvement of the Werner's syndrome protein in the signal transduction pathway by which caffeine could override the DNA damage induced G2 checkpoint Description: L'articolo è disponibile sul sito dell'editore: http://informahealthcare.com Thu, 31 Dec 1998 23:00:00 GMT http://hdl.handle.net/2067/1717 1998-12-31T23:00:00Z