Compound 48/80 impairs cytokinesis in murine leukemiccells

Darzynkiewicz, Zbigniew; Carter, Sally

doi:10.1002/jcp.1041190102

Cited by 8 publications

(3 citation statements)

References 12 publications

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“…On the other hand, many authors who have studied antiproliferative drugs have linked this effect to an action on a specific phase of the cell cycle. This, for example, is the case for dexamethasone, which leads to an accumulation of NHIK 3025 cells in GO11 (Bakke and Eiknes, 1981)) or the compound 48/80 (Darzynkiewicz and Carter, 1984), which produces an increase in the percentage of binucleate L 1210 cells. However, other molecules exhibit complex action-sodium butyrate, for example, leads to two different actions for the same cellular type (rabbit articular chondrocyte): an effect on GOD after 24-h treatment and on G2 and cytokinesis after 72-h treatment (Larno et al, 1984).…”

Section: Discussionmentioning

confidence: 96%

Differential effect of D‐penicillamine on the cell kinetic parameters of various normal and transformed cellular types

Friteau

Jaffray

Ronot

et al. 1988

Journal Cellular Physiology

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The cell-growth-inhibitory and phase-specific effects of D-penicillamine on cell-cycle progression were investigated using cell-proliferation patterns, quantitative cell-cycle analysis by flow cytometry, and determination of the mitotic index and binucleate cell fraction of normal (rabbit articular chondrocytes, L 809, rabbit fibroblasts) and transformed (HeLa, L 929) cells. D-penicillamine treatment resulted in an inhibition of growth within a dose range of 5 x 10(-4) M to 7.5 x 10(-3) M. Examination of DNA by flow cytometric analysis revealed that rabbit articular chondrocytes were preferentially arrested in the G0/1 phase of the cell cycle, whereas the other cell lines were blocked in the G2 + M phase; the increase in the proportion of cells with G2 + M DNA content was partially due to an enhancement of binucleate cells, resulting in a cytokinesis perturbation for HeLa and L 929 cells. These results showed that D-penicillamine affects cell proliferation through different events according to cell type.

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Section: Discussionmentioning

confidence: 96%

Differential effect of D‐penicillamine on the cell kinetic parameters of various normal and transformed cellular types

Friteau

Jaffray

Ronot

et al. 1988

Journal Cellular Physiology

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“…Compound 48/80 is a mixture of synthetic polymers derived from N-methyl-methoxy-phenylethylamine, and because of its ability to interact with plasma membrane and induce cell degranulation is widely used in studies of mast cells and eosinophils. 13,15 In fact, we have already observed before 16 that compound 48/80 can impair cytokinesis of murine leukemic cells, but at that time no mechanistic explanation for this phenomenon was provided. It should be noted that compound 48/80, which at the concentration presently used showed no detectable toxicity to the studied cells, induced cell adherence not only when applied for slide precoating but also when added directly into the cultures.…”

Section: Discussionmentioning

confidence: 99%

Enforced Adhesion of Hematopoietic Cells to Culture Dish Induces Endomitosis and Polyploidy

Huang

Dai²,

Darżynkiewicz³

2005

Cell Cycle

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Cells of epithelial or endothelial lineage when forced to grow in suspension undergo the detachment-induced death termed "anoikis". In the present study we explored the reverse situation, namely the effect of enforcement of hematopoietic lineage cells that are normally maintained in suspension to grow attached. Towards this end murine L1210 or human HL-60 and Jurkat leukemia cells were cultured in slide chambers coated with poly-L-or poly-D-lysine, or with compound 48/80, the polycations attracting them electrostatically. Within minutes after the transfer L1210 cells strongly adhered to bottom surface of the dish and shortly thereafter binuclear, and later on, polynuclear cells become apparent. The frequency of nuclei per cell increased with time and polykaryons with up to 16 nuclei and high DNA ploidy (DI = 16.0) were apparent after 48 h. After 4 days the size (volume) of some polykaryons exceeded by over 340-fold the volume of mononuclear cells. The presence of mitotic figures and abnormal mitotic spindles in adhering polykaryons provided evidence of the impeded cytokinesis that led to endomitosis. Most polykaryons excluded trypan blue, had balanced growth (unchanged protein/DNA ratio compared to monokaryons), and showed no evidence of apoptosis. Individual nuclei within each polykaryon replicated DNA in synchrony. The strong cell attachment and aborted cytokinesis were cell line specific since no significant endomitosis was observed in Jurkat-or HL-60-cells which did not strongly attach to polycation-coated surfaces. Defective cytokinesis and induction of polyploidy by this mechanism, if it occurs in vivo (e.g., mediated by integrins), may lead to aneuploidy and therefore have tumorigenic consequences. The phenomenon offers a novel experimental model for induction of polyploidy and provides an alternative to cytocholasin B to prevent cytokinesis in the mutagenicity cytokinesis-blocked micronucleus (CBMN) assay.

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“…The production of binucleate cells is, therefore, another cellular state of potential usefulness in answering genetic and physiological questions. Binucleate mammalian cells can be induced by various treatments such as cytochalasin B (11,1'7), compound 48/80 (8), or cis DDP (5). Although the mechanisms for the drug action are not clearly understood, a major consequence is inhibition of the completion of cytokinesis.…”

Section: Discussionmentioning

confidence: 99%

G2 arrest, binucleation, and single‐parameter DNA flow cytometric analysis

et al. 1986

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One important facet of flow cytometry involves the effects of pharmacological agents on cell cycle progression. Comparative G2 fraction perturbations were examined: effects of sodium butyrate on articular chondrocytes, effects of an antineoplastic agent (SOAz) and an antirheumatic drug (D‐penicillamine) on HeLa cells. Even though DNA flow cytometric analysis detects preferentially an induction of G2 arrest, the mode of action of these agents on the cell cycle is different. Sodium butyrate and D‐penicillamine lead to an increase of binucleate cells due to cytokinesis perturbation. Because of similar fluorescence intensity, distinguishing G2 from binucleate GO/1 cells is not easily possible using DNA content measurement and reflects a failure of flow cytometry in the detection of binucleate cells. Rapid cell cycle analysis of single cells should contribute greatly to the study of pharmacological interactions, but DNA flow cytometric measurements obtained from cultured cells exposed to certain agents must be cautiously interpreted because those may interact on cytokinesis and induce artefacts in histogram interpretation.

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Compound 48/80 impairs cytokinesis in murine leukemiccells

Cited by 8 publications

References 12 publications

Differential effect of D‐penicillamine on the cell kinetic parameters of various normal and transformed cellular types

Differential effect of D‐penicillamine on the cell kinetic parameters of various normal and transformed cellular types

Enforced Adhesion of Hematopoietic Cells to Culture Dish Induces Endomitosis and Polyploidy

G2 arrest, binucleation, and single‐parameter DNA flow cytometric analysis

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