Immortalized phenotype and the presence of active oncogenes correlate with the capacity of culture cells to induce reactivation of DNA synthesis in macrophage nuclei in heterokaryons

Prudovsky, Igor; Gumeniuk, Raphilja R.; Yegorov, Yegor E.; Poletayev, A.I.; Chumakov, Peter M.; Zelenin, A. V.

doi:10.1016/0922-3371(89)90753-3

Cited by 7 publications

(5 citation statements)

References 21 publications

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“…If this is true, macrophages do not need any intracellular diffusable replication inhibitors evidently existing in neutrophils. Actually, macrophages are unable to inhibit DNA synthesis in the nuclei of non-malignant cells (Prudovsky et al 1985). Summarizing the data from our work on neutrophils and the earlier data on macrophages we can conclude that, despite a close kinship, these two types of differentiated cells may employ different mechanisms for proliferation blockage.…”

Section: Control Cyclohexirnidesupporting

confidence: 64%

“…In preliminary experiments attempts were made to obtain PEG-induced and Sendai-induced cell fusion. A modification of the PEG-induced fusion method, very efficient for macrophages (Prudovsky et al 1985), gave a low yield of heterokaryons between neutrophils and culture cells (less than 4% heterokaryons in preparations). The Sendai virus-induced fusion (for details see Prudovsky et al 1990) was also not efficient for neutrophils (5-6% heterokaryons).…”

Section: Cell Fusionmentioning

confidence: 99%

“…that the presence of active immortalizing oncogenes in proliferating cells enables the activation of DNA synthesis in the macrophage (Prudovsky et al 1989a). A hypothesis has been proposed in which some changes in the macrophage genome prevent replication and that the elimination, or neutralization, of these changes by the products of immortalizing oncogenes takes place (Zelenin & Prudovsky 1989).…”

Section: Control Cyclohexirnidementioning

confidence: 99%

“…In this work a detailed analysis of heterokaryon DNA synthesis blockage in neutrophils has been carried out. The neutrophils are of particular interest because, in the course of differentiation, they have common precursors with macrophages-whose behaviour in heterokaryons has been previously studied in detail (Prudovsky, Yegorov & Zelenin 1985, Prudovsky et al 1989a. The following questions have been asked in this investigation:…”

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confidence: 99%

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The control of DNA replication in hybrids between neutrophils and fibroblasts

et al. 1993

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DNA synthesis regulation in heterokaryons between mouse neutrophils and cultured cells of various proliferative potentials has been studied. The following features have been found. Both immortalized and non-immortalized cells can reactivate DNA synthesis in neutrophil nuclei. The reactivation ability of cultured cells increases after immortalization and is not changed by further transformation. Neutrophils inhibit the entry of cultured cell nuclei into S phase and have no effect on ongoing DNA synthesis. Malignant cells are much less sensitive to the inhibitory action of neutrophils than non-malignant ones. Non-malignant immortalized cells are as sensitive to this effect as non-immortalized cells. Neutrophil karyoplasts do not influence DNA synthesis in partner cultured cell nuclei. Cycloheximide pretreatment of neutrophils drastically diminishes their inhibitory effect.

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Section: Control Cyclohexirnidesupporting

confidence: 64%

Section: Cell Fusionmentioning

confidence: 99%

Section: Control Cyclohexirnidementioning

confidence: 99%

mentioning

confidence: 99%

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The control of DNA replication in hybrids between neutrophils and fibroblasts

et al. 1993

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“…The case is somewhat different with the macrophage nuclei in heterokaryons. It was shown (Yegorov et al , 1984;Prudovsky et al , 1989) that only "immortalized" cells, capable of unlimited proliferation in a culture, could in duce DNA synthesis in macrophage nuclei upon fusion.…”

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confidence: 99%

Role of Telomerase in Reactivation of Macrophage Nuclei in Heterokaryons

Дашинимаев

et al. 2005

Russ J Dev Biol

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It was shown that the duration of stay of macrophages in the peritoneal cavity of mice and method of their isolation did not affect markedly their capacity for resumption of DNA synthesis in heterokaryons. This means that mouse macrophage undergo such changes during differentiation that reactivation of DNA synthesis in their nuclei is only possible after interaction of telomeres with telomerase, since it was already shown that telomerase was involved in reactivation of DNA synthesis in the macrophage nuclei. The results of experiments did not reveal differences in the length of telomeres in mouse macrophages and other somatic cells. This could depend on the significant length of mouse telomeres and, as a result, their shortening, sufficient for the inhibition of proliferation, is beyond the limits of sensitivity of the current methods. It is also possible that changes in DNA properties in the macrophages occurring during their differentiation depend on changes in the conformation of the telomere complex in these cells. Testing of this suggestion is relevant with respect to recent data that cell hybridization, specifically in the form of heterokaryons, may be essential in realization of the therapeutic effect caused by the introduction of cells during cell therapy.

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Resident macrophages specifically inhibit DNA synthesis in the nuclei of transformed cells in heterokaryons

Prudovsky

Gumeniuk

Yegorov

et al. 1989

Intl Journal of Cancer

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DNA synthesis in heterokaryons of mouse peritoneal macrophages and various proliferating cultured cells was analyzed. Macrophages did not inhibit replication in the nuclei of non-immortalized and spontaneously immortalized cells (rat fibroblasts and macrophages, mouse pre-macrophages, NIH3T3 cells). On the contrary, the percentage of DNA-synthesizing nuclei of malignant HeLa cells was drastically reduced in heterokaryons. The transformation of NIH3T3 cells with c-Ki-ras oncogene and that of rat chondrocytes with p53 oncogene made these cells sensitive to the replication-inhibiting activity of macrophages in heterokaryons. Our observation represents a kind of "intracellular" cytotoxic activity of macrophages directed against transformed cells.

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Immortalized phenotype and the presence of active oncogenes correlate with the capacity of culture cells to induce reactivation of DNA synthesis in macrophage nuclei in heterokaryons

Cited by 7 publications

References 21 publications

The control of DNA replication in hybrids between neutrophils and fibroblasts

The control of DNA replication in hybrids between neutrophils and fibroblasts

Role of Telomerase in Reactivation of Macrophage Nuclei in Heterokaryons

Resident macrophages specifically inhibit DNA synthesis in the nuclei of transformed cells in heterokaryons

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