Butyrate does not induce single strand breaks in friend erythroleukemia cells or in 3T6 mouse fibroblasts

Wintersberger, Erhard; Mudrak, Ingrid

doi:10.1016/0014-5793(82)80445-6

Cited by 12 publications

(3 citation statements)

References 17 publications

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“…In recent years, it has been argued that the induction of MELC differentiation may involve DNA single-strand scission (Terada et al, 1978;Scher & Friend, 1978). This has not been confirmed by us or others (Pantazis et al, 1981;Wintersberger & Mudrak, 1982;Reboulleau et al, 1983), and a likely alternative involves conformational changes of the chromatin that could be mediated by certain postsynthetic modifications of its constituent molecules. Recently, Reczek et al (1982) have been able to show that butyrate-treated HeLa cells do exhibit certain changes in chromatin structure.…”

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confidence: 73%

Chemical inducers of differentiation cause conformational changes in the chromatin and deoxyribonucleic acid of murine erythroleukemia cells

Reboulleau¹,

Shapiro²

1983

Biochemistry

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The chemical inducers of murine erythroleukemia cell differentiation, dimethyl sulfoxide, sodium butyrate, and ethionine, elicited conformational changes in the DNA and chromatin of treated cells. The chromatin from dimethyl sulfoxide treated and butyrate-treated cells exhibited circular dichroic spectra different from that of the noninduced control. The molar ellipticity [theta]282.5 in isotonic saline decreased from 4900 deg X cm2 X dmol-1 for control chromatin to 3800 and 3600 deg X cm2 X dmol-1 for dimethyl sulfoxide treated and butyrate-treated chromatin, respectively, while that from ethionine-treated chromatin remained virtually unchanged (5400 deg X cm2 X dmol-1). Increasing the ionic strength to 2.5 or 5 M with NaCl resulted in a substantial, uniform, decrease in molar ellipticity. Thermal denaturation profiles of high molecular weight DNA prepared from each of the inducer-treated cells showed a pronounced hyperchromic shift but no change in Tm when compared to control DNA. Circular dichroic spectra of the DNA indicated a decrease in ellipticity [theta]277 from 9600 deg X cm2 X dmol-1 to 8900, 8300, and 8800 deg X cm2 X dmol-1 for ethionine, dimethyl sulfoxide, and butyrate treated cells, respectively. Treatment of the DNA with 3 M NaCl canceled the UV and CD differences. These measurements indicate an increased stacking of bases or an increased compactness of the DNA from induced cells. Concomitant with specific modifications such as hypomethylation of DNA, the data can be interpreted in terms of conformational changes in chromatin resulting from core histone acetylation.

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confidence: 73%

Chemical inducers of differentiation cause conformational changes in the chromatin and deoxyribonucleic acid of murine erythroleukemia cells

Reboulleau¹,

Shapiro²

1983

Biochemistry

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“…Thus fragment joining is particularly sensitive to inhibition of translation, changes in availability of deoxynucleotides or impaired activity of DNA polymerase-a. Ligation of nascent DNA is also influenced by the availability of polyamines [36], by agents which induce DNA damage [37] and by the activity of poly(ADP-ribose) polymerase [38,39]. In our system interferons could affect any one of these mechanisms to cause transient accumulation of Okazaki fragments.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of cell proliferation by interferons

Moore

Gewert

Clemens

1984

European Journal of Biochemistry

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The inhibition of proliferation of Daudi cells in culture by human interferons is characterized by a change in the kinetics of labelling of different size classes of newly synthesized DNA. Initially, labelled precursors are incorporated exclusively into small DNA (Okazaki fragments) in both control and interferon-treated cells, as revealed by alkaline sucrose gradient centrifugation. In the interferon-treated cells, there is enhanced labelling of this small DNA after short periods of incorporation and slower conversion to larger DNA size classes, in comparison with the DNA of control cells. This effect is apparent after 12 h of interferon treatment, coincident with the onset of the inhibition of cell proliferation. It becomes progressively more marked up to 4 days, by which time cell growth has ceased completely.Experiments using bromodeoxyuridine as a density label and analysis of radioactive DNA on caesium chloride/caesium sulphate gradients also reveal that some newly replicated DNA may be unstable and may turn over within a few hours of its synthesis. The label derived from DNA breakdown is efficiently reincorporated into newly synthesized molecules. It is suggested that interferon treatment inhibits DNA replication by activating DNA turnover rather than by directly inhibiting synthesis. This effect, together with the progressive retardation of conversion of Okazaki fragments to larger DNA, may lead to the eventual failure of cell proliferation.Highly purified preparations of mammalian interferons have been shown to exert multiple biological effects on their target cells. In addition to the widely studied inhibition of viral replication, the anticellular actions of both naturally occurring [I -31 and cloned interferon species [4] are of considerable interest. There is, however, very little information concerning the molecular mechanisms by which the replication of the cellular genome is regulated during growth inhibition by interferons. Some studies have suggested an inhibition of DNA synthesis, based on impaired incorporation of [3H]thymidine, but at least in some cases this reflects severely impaired thymidine uptake and thymidine kinase activity rather than a true effect on DNA replication [5 -81. We are carrying out a detailed analysis of the changes in cellular functions which may be responsible for the antiproliferative effect of human interferons on Daudi cells in culture.Daudi cells are human lymphoblastoid cells containing multiple copies of the Epstein-Barr virus genome. They are highly sensitive to the inhibitory effects of interferons on cell growth [7, 9-111 and treatment with 100 units/ml of a-interferons causes a 40 -50 % inhibition in the rate of cell proliferation after two days [8]. There is, however, no more than a 10 -15 % inhibition of the overall rate of DNA synthesis per lo6 cells after this period of treatment, as measured by flooding the intracellular dTTP pool with excess labelled thymidine or by assessing incorporation of [3H]dCTP into DNA in permeabilized and lysed cell systems [I...

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“…The inhibition effect of butyrate on cell division was, however, considered to be independent of its hyperacetylation effect (Rubenstein et al, 1979). Recent results on the efiects of butyrate on the cell cycle suggest that cells are specifically blocked in the G1 period (Fallon and Cox, 1979;D'Anna et al, 1980;Wijk et al, 1981;Darzynkiewicz et al, 1981;Xue and Rao, 1981;Wintersberger and Mudrak, 1982). The rate of cell-cycle progression through G2-M and through S can, however, also be altered.…”

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Effects of sodium butyrate on growth and cell‐cycle kinetics of cultured rabbit articular chondrocytes

Larno

Ronot

Adolphe

et al. 1984

Journal Cellular Physiology

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The sodium salt of n-butyric acid was found to inhibit the growth of asynchronous cultures of rabbit articular chondrocytes. This inhibitory effect was dose-dependent between 1 mM and 5 mM, reversible, and accompanied by volume enhancement and modification of cellular morphology. Flow-cytometric analysis showed that drug exposure led to a slowing-down of the cell-cycle progression; after 1 day's exposure, cells accumulated in G1, and after 2 or 3 days' treatment, in G2, without a blockage in M; the increase of cells in G2 was in fact due to an enhancement of binculeated cells. The treated cells had an increased RNA content. Articular chondrocytes seem to be target cells for sodium butyrate and therefore it represents a valuable biological tool for studying the mechanisms of their growth regulation.

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Butyrate does not induce single strand breaks in friend erythroleukemia cells or in 3T6 mouse fibroblasts

Cited by 12 publications

References 17 publications

Chemical inducers of differentiation cause conformational changes in the chromatin and deoxyribonucleic acid of murine erythroleukemia cells

Chemical inducers of differentiation cause conformational changes in the chromatin and deoxyribonucleic acid of murine erythroleukemia cells

Inhibition of cell proliferation by interferons

Effects of sodium butyrate on growth and cell‐cycle kinetics of cultured rabbit articular chondrocytes

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