Radiation sensitivity of human B-lineage lymphoid precursor cells

Uckun, Fatih M.; Mitchell, James B.; Obuz, Vedat; Park, Chae Heonjoo; Waddick, Kevin G.; Friedman, Norman R.; Oubaha, Lahcen; Min, Woo Sung; Song, Chang W.

doi:10.1016/0360-3016(91)90332-x

Cited by 30 publications

(9 citation statements)

References 40 publications

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“…MSH2 has been implicated in a variety of processes that serve to protect the genome integrity like DNA repair, cell cycle checkpoints and apoptosis [22]. The specific protein has been shown to be implicated also in several other pathways like DSB repair [24] and has been associated with radiosensitivity and accumulation of oxidative DNA lesions like 8-oxodG [25][26][27][28]. Defects in MSH2 have been associated with several childhood leukemias including ALL [29,30].…”

Section: Introductionmentioning

confidence: 99%

Compromised repair of clustered DNA damage in the human acute lymphoblastic leukemia MSH2-deficient NALM-6 cells

Holt

Scemama

Panayiotidis

et al. 2009

Mutation Research/Genetic Toxicology and Environmental Mutagene

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Section: Introductionmentioning

confidence: 99%

Compromised repair of clustered DNA damage in the human acute lymphoblastic leukemia MSH2-deficient NALM-6 cells

Holt

Scemama

Panayiotidis

et al. 2009

Mutation Research/Genetic Toxicology and Environmental Mutagene

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“…We used the fetal liver pro-B cell line FL112, the pre-pre-B cell line Reh, the pre-B cell line Nalm-6, and the early B/Burkitt lymphoma cell lines Daudi, Ramos, and Ramos-1 (a subclone of Ramos). The immunophenotypic and genotypic features and the radiation sensitivity of these human B-lymphocyte precursor cell lines were detailed in a previous report (8). We also used primary bone marrow blasts from a pre-pre-B acute lymphoblastic leukemia patient (UPN10), following the guidelines of the University of Minnesota Committee on the Use of Human Subjects in Research for secondary use of pathologic or surgical tissue.…”

Section: Methodsmentioning

confidence: 99%

“…Cells (5 x i05 per ml in plastic tissue culture flasks) were irradiated (137Cs irradiator; J. L. Shephard, Glendale, CA, model Mark I) with 100-400 cGy at a dose rate of 99 cGy/min during logarithmic phase and under aerobic conditions, as previously described (8,9). Prior to irradiation, cells were incubated for 1 hr at 37°C with (a) phosphate-buffered saline, (b) the PTK inhibitor genistein ,g/ml = 37-370 ,uM; ICN), (c) the protein kinase C inhibitor 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H7; 11 ,ug/ml = 30 ,M; GIBCO BRL), or (d) the protein-tyrosine-phosphatase (PTPase) inhibitor sodium orthovanadate (10-100 ,M, Sigma) or for 24 hr at 37°C with the benzoquinoid ansamycin antibiotic herbimycin A (7 ,g/ml = 12 ,uM; GIBCO/BRL), a potent PTK inhibitor, using previously described protocols (6,7).…”

Section: Methodsmentioning

confidence: 99%

Ionizing radiation stimulates unidentified tyrosine-specific protein kinases in human B-lymphocyte precursors, triggering apoptosis and clonogenic cell death.

Uckun

Tuel‐Ahlgren

Song

et al. 1992

Proc. Natl. Acad. Sci. U.S.A.

173

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Very little is known regarding the effects of ionizing radiation on cytoplasmic signal transduction pathways.Here, we show that ionizing radiation induces enhanced tyrosine phosphorylation of multiple substrates in human B-lymphocyte precursors. This response to ionizing radiation was also observed in cells pretreated with vanadate, a potent proteintyrosine-phosphatase (PTPase) inhibitor, and phosphotyrosyl [Vals]angiotensin II phosphatase assays showed no decreased PTPase activity in irradiated cells. Thus, enhanced tyrosine phosphorylation in irradiated B-lymphocyte precursors is not triggered by inhibition of total cellular PTPase activity. Immune-complex kinase assays using anti-phosphotyrosine antibodies demonstrated enhanced protein-tyrosine kinase (PTK) activity in the immunoprecipitates from irradiated cells, and the PTK inhibitors genistein and herbimycin effectively prevented radiation-induced tyrosine phosphorylation. Immune-complex kinase assays on irradiated and unirradiated B-lymphocyte precursors using antibodies prepared against unique amino acid sequences of pv9nf, p56/p53'Yn, p55""', and p561ck demonstrated that these Src-family tyrosine kinases were not the primary PTKs responsible for enhanced tyrosine kinase activity in the anti-phosphotyrosine antibody immunoprecipitates or for enhanced tyrosine phosphorylation of multiple substrates. Thus, our fmdings favor the hypothesis that ionizing radiation induces enhanced tyrosine phosphorylation in B-lymphocyte precursors by stimulation of as yet unidentified PTKs. Tyrosine phosphorylation appears to be an important proximal step in radiationinduced apoptosis and clonogenic cell death because inhibition of PTK prevents DNA fragmentation and loss of clonogenicity of irradiated B-lymphocyte precursors. Since PTKs play myriad roles in the regulation of cell function and proliferation, the activation of a PTK cascade, as detailed in this report, may explain some of the pleiotropic effects of ionizing radiation on cellular functions of B-lymphocytes and their precursors.The molecular mechanism by which ionizing radiation inhibits and destroys mammalian cells has been widely explored but not precisely deciphered (1, 2). Protein-tyrosine kinases (PTKs) participate and likely play pivotal roles in initiation of signal cascades that affect proliferation and survival of human B-lymphocyte precursors (3-7). The purpose of this study was to examine the effects of ionizing radiation on PTKs in human B-lymphocyte precursors at discrete developmental stages of B-cell ontogeny.MATERIALS AND METHODS Patient Material and Cell Lines. We used the fetal liver pro-B cell line FL112, the pre-pre-B cell line Reh, the pre-B cell line Nalm-6, and the early B/Burkitt lymphoma cell lines Daudi, Ramos, and Ramos-1 (a subclone of Ramos). The immunophenotypic and genotypic features and the radiation sensitivity of these human B-lymphocyte precursor cell lines were detailed in a previous report (8). We also used primary bone marrow blasts from a pre-pre-B acute lymphoblas...

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“…Lymphomas often die by apoptosis, but the clonogenic survival differs considerably between tumors of this type. 3,4 More knowledge about the molecular mechanisms underlying these differences in radiosensitivity would be useful in the design of improved treatment strategies based on IR for lymphomas. 5 The radiation response is thought to be the result of changes in the transcription of genes that are involved in DNA repair, cell cycle checkpoints and induction of cell death.…”

mentioning

confidence: 99%

Response of malignant B lymphocytes to ionizing radiation: Gene expression and genotype

Lyng

Landsverk

Kristiansen

et al. 2005

Intl Journal of Cancer

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The human malignant B-lymphocyte cell lines Reh and U698 show arrest in G 2 phase after ionizing radiation (IR), but only Reh cells arrest in G 1 phase and die by apoptosis. We have used cDNA microarrays to measure changes in gene expression at 2, 4 and 6 hr after irradiation of Reh and U698 cells with 0.5 and 4 Gy in order to begin exploring the molecular mechanisms underlying the phenotypic changes. We also investigated whether gene expression changes could be caused by possible aberrations of genes, as measured by comparative genomic hybridization. Reh cells showed upregulation of CDKN1A that likely mediated the G 1 arrest. In contrast, U698 cells have impaired function of TP53 protein and no activation of CDKN1A, suppressing the arrest in G 1 . The G 2 arrest in both cell lines was likely due to repression of PLK1 and/or CCNF. IR-induced apoptosis in Reh cells was probably mediated by TP53 and CDKN1A, whereas a high expression level of MCL1, caused by gene amplification, and activation of the NFKB pathway may have suppressed the apoptotic response in U698 cells. Genes suggested to be involved in apoptosis were activated long before this phenotype was detectable and showed the same temporal expression profiles as genes involved in cell cycle arrest. Our results suggest that differences in functionality and/or copy number of several genes involved in IR-regulated pathways contributed to the phenotypic differences between Reh and U698 cells after IR, and that multiple molecular factors control the radiation response of malignant B lymphocytes. ' 2005 Wiley-Liss, Inc.

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Radiation sensitivity of human B-lineage lymphoid precursor cells

Cited by 30 publications

References 40 publications

Compromised repair of clustered DNA damage in the human acute lymphoblastic leukemia MSH2-deficient NALM-6 cells

Compromised repair of clustered DNA damage in the human acute lymphoblastic leukemia MSH2-deficient NALM-6 cells

Ionizing radiation stimulates unidentified tyrosine-specific protein kinases in human B-lymphocyte precursors, triggering apoptosis and clonogenic cell death.

Response of malignant B lymphocytes to ionizing radiation: Gene expression and genotype

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