Radiation-induced Interphase Death of Rat Thymocytes is Internally Programmed (Apoptosis)

Yamada, Takeshi; Ohyama, Harumi

doi:10.1080/09553008814550431

Cited by 214 publications

(53 citation statements)

References 7 publications

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“…We have argued elsewhere that entry to apoptosis requires two cellular events: 'priming', in which the effector proteins for apoptosis accumulate within the cell, and 'triggering', in which these proteins are activated (Arends & Wyllie, 1991;Dive & Wyllie, 1993 Yamada & Ohyama, 1988;Smith et al, 1989;Walker et al, 1991). These stimuli have clearly different initial effects upon the thymocyte, as shown by the fact that calcium signalling (McConkey et al, 1989a and1989b) and p53 dependence (Clarke et al, 1993) are features of some but not all of them.…”

Section: Susceptibility To Apoptosis Reflects Availability Of Endonucmentioning

confidence: 99%

Susceptibility to apoptosis is differentially regulated by c-myc and mutated Ha-ras oncogenes and is associated with endonuclease availability

Arends

Mcgregor²,

Toft³

et al. 1993

Br J Cancer

115

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Summary Oncogenes and oncosuppressors can derugulate cell replication in tumours, and recently have been shown to influence the probability of apoptosis. The effects of human c-myc and mutated (T24) Ha-ras oncogenes on susceptibility to apoptosis were investigated by introducting them into immortalised rat fibroblasts. The resulting family of transfectants showed closely similar measures of proliferation, but widely divergent rates of apoptosis, differing by up to fifteen-fold, that correlated inversely with population expansion rates in vitro. T24-ras transfectants with moderate or high p2lras expression showed reduced apoptosis, and this was reversed by pharmacological inhibition of membrane localisation of p2l's by mevinolin. In contrast, c-myc stimulated apoptosis, and this was further enhanced by serum deprivation. Inducibility of effector proteins represents one possible mechanism of genetic control of the susceptibility to apoptosis, and its investigation showed that c-myc was associated with expression by viable cells of latent calcium/magnesium sensitive endonuclease activity characteristic of apoptosis. In contrast, endonuclease activity was not detected in viable cells of a T24-ras transfectant expressing high levels of p2lras. Thus, there appeared to be differential regulation of susceptibility to apoptosis, positively by c-myc and negatively by activated ras, and this was associated with availability of endonuclease activity. Genetic modulation of apoptosis in human neoplasms is likely to influence net growth rate, retention of cells acquiring new mutations and response to certain chemotherapeutic agents.

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Section: Susceptibility To Apoptosis Reflects Availability Of Endonucmentioning

confidence: 99%

Susceptibility to apoptosis is differentially regulated by c-myc and mutated Ha-ras oncogenes and is associated with endonuclease availability

Arends

Mcgregor²,

Toft³

et al. 1993

Br J Cancer

115

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show abstract

“…In contrast to mitotic cell death, apoptosis is a relatively rapid and irreversible process which occurs within a few hours following IR exposure. Although documented in proliferating cell lines as well as tumor cells (Bump et al, 1994), IR-induced apoptosis was originally described in nonmitotic cells such as lymphocytes, which lead to the term of interphase cell death (Yamada and Ohyama, 1988;Soldatenkov et al, 1989).…”

Section: Introductionmentioning

confidence: 99%

Lack of ceramide generation in TF-1 human myeloid leukemic cells resistant to ionizing radiation

et al. 1998

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The mechanism(s) by which ionizing radiation (IR) induces cell death is of fundamental importance in understanding cell sensitivity and resistance. Here we evaluated the response to IR of two subclones of the autonomous human erythromyeloblastic cell line TF-1: TF-1-34 (which expresses CD34) and TF-1-33 (which lacks CD34). In clonogenic assays, TF-1-34 cells were found to be relatively less sensitive to IR compared to TF-1-33 cells based on the D 0 determination (3.01 vs 1.56 Gy). Furthermore, after IR at 12 Gy, TF-1-33 cell viability decreased by *50% within 24 h, whereas TF-1-34 cell growth was unaffected during this time. Gradual loss of TF-1-34 cell viability was observed only after 48 h. Morphological and molecular analysis revealed that TF-1-33 cells died of apoptosis, and TF-1-34 cells of delayed reproductive cell death. While IR produced comparable amounts of DNA double strand breaks (DSB) in both cell lines, TF-1-34 retained DSB much longer than TF-1-33 suggesting that radioresistance and the defective apoptotic response of TF-1-34 cells was not related to a higher DNA repair capacity. However, the lack of an apoptotic response in TF-1-34 was correlated to the absence of a sphingomyelin (SM)-ceramide (CER) signaling pathway. Indeed, IR triggered in TF-1-33 cells but not in TF-1-34, SM hydrolysis (25% at 12 Gy) and CER generation (450%) through the activation of neutral but not acid sphingomyelinase. Synthetic cell permeate CER induced apoptosis in both TF-1-33 and TF-1-34 cells. This study indicates that alterations of the SM-CER signaling pathway can significantly influence the cell death process as well as the survival of acute myeloid leukemia cells after IR exposure.

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“…However, lethal cellular programs that lead to apoptosis may also be triggered by a variety of exogenous or environmental stimuli. Some of these are cell type specific, including glucocorticoid-dependent lymphocyte killing (6), antigen receptor-associated thymocyte death (7,8) and TGF-B-induced hepatocyte death, whereas others are effective on a broad range of cells, including target cell lysis by cytotoxic T cells (9), radiation-induced DNA damage (10,11) and engagement of specific cell surface receptors by natural ligands or antibodies (3,4). Recently, three structurally related cell surface receptors implicated in transduction of death signals in a broad range of cell types have been identified and characterized.…”

mentioning

confidence: 99%

Fas and tumor necrosis factor receptor-mediated cell death: similarities and distinctions.

Clément

Stamenkovic

1994

The Journal of Experimental Medicine

140

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SummaryFas antigen and two tumor necrosis factor receptors (TNFR), p55 and p75, are implicated in the triggering of cell death upon stimulation by natural ligands and specific monoclonal antibodies. However, the relative efficiency of each receptor, the mechanisms that regulate their function and the signaling pathways they employ, remain to be elucidated. In this study, fusion proteins, composed of the extracellular domain of CD40 and the intracellular and transmembrane domains of Fas, TNFRp55 and TNFRp75, were stably expressed in a human melanoma cell line that is deficient in Fas and TNFR expression. Transfectants were stimulated by a soluble recombinant form of the CD40 ligand gp39, and the effect on cell viability determined. Engagement of all three fusion proteins by the gp39 ligand induced lethal signals, but the rate at which cell death occurred was distinct. Fas-derived signals were observed to have the most rapid effect, killing most cells within hours of stimulation, whereas TNFILp55-and TNFILp75-associated signals resulted in cell death within 2-3 d after engagement by ligand. It is interesting to note that optimal cell killing by all three fusion proteins was dependent on a critical, low to intermediate, cell surface expression level. High levels of fusion protein expression, on the other hand, were associated with inhibition of cell death. Our results provide a model to study Fas and TNFRmediated cell death and suggest a novel mechanism for the regulation of death signals triggered by members of the TNFR family.

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Radiation-induced Interphase Death of Rat Thymocytes is Internally Programmed (Apoptosis)

Cited by 214 publications

References 7 publications

Susceptibility to apoptosis is differentially regulated by c-myc and mutated Ha-ras oncogenes and is associated with endonuclease availability

Susceptibility to apoptosis is differentially regulated by c-myc and mutated Ha-ras oncogenes and is associated with endonuclease availability

Lack of ceramide generation in TF-1 human myeloid leukemic cells resistant to ionizing radiation

Fas and tumor necrosis factor receptor-mediated cell death: similarities and distinctions.

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