Antonius W.T. Konings

University of Groningen

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Harm H. Kampinga

University of Groningen

Robert P. Coppes

University Medical Center Groningen

Herman J. Woerdenbag

University of Groningen

Arjan Vissink

University Medical Center Groningen

Peter van Luijk

University Medical Center Groningen

Jacobus Maarten Schippers

Paul Scherrer Institute

Willy Lemstra

University Medical Center Groningen

Aäron C. Beekman

University of Groningen

Niesko Pras

Pharmac

Albert J. van der Kogel

University of Wisconsin–Madison

Cooperative Institutions

University of Groningen

University Medical Center Groningen

Leiden University

Radboud University Nijmegen

Utrecht University

National Institute for Public Health and the Environment

University of Amsterdam

Vrije Universiteit Amsterdam

University Medical Center Utrecht

Dialyse Centrum Groningen

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Cytoxicity and Mode of Action of Aeroplysinin-1 and a Related Dienone from the Sponge Aplysina aerophoba

Journal of Natural Products (1996)

Albert Koulman Peter Proksch Rainer Ebel Aäron C. Beekman Wim van Uden

Aeroplysinin-1 (1) and the structurally related dienone 2 were cytotoxic to Ehrlich ascites tumor (EAT) cells and HeLa tumor cells in the microculture tetrazolium (MTT) and clonogenic assays. Both compounds are bromotyrosine derivatives, isolated from the marine spong Aplysina aerophoba. As the effective concentrations in the MTT assay were lower than in the clonogenic assay, 1 and 2 are able to cause growth inhibition as well as actual cell death in these cell lines. With an IC50 value of 8.2 μM (MTT assay, 2-h incubation, EAT cells), 1 was the more toxic compound. When the cells were depleted of glutathione by pretreatment with buthionine sulfoximine, they were significantly more sensitive toward 1 and 2 in the MTT assay. A dose-enhancement factor as high as 11.8 was found in EAT cells after 2-h incubation with 2. Using electron paramagnetic resonance we were able to measure free radical formation of 1 and 2, yielding the semiquinone structures 3 and 4, respectively, in a culture medium with tumor cells. It is concluded that free radicals are, at least in part, responsible for the cytotoxicity of 1 and 2. This conclusion is in line with expectations derived from the chemical structures of both compounds.

Sponge

10.1021/np960167z

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Citations (58)

Radiation-induced Lipid Peroxidation: Influence of Oxygen Concentration and Membrane Lipid Composition

International Journal of Radiation Biology and Related Studies in Physics Chemistry and Medicine (1987)

H. Wolters C. A. M. van Tilburg Antonius W.T. Konings

Radiation-induced lipid peroxidation in phospholipid liposomes was investigated in terms of its dependence on lipid composition and oxygen concentration. Non-peroxidizable lipid incorporated in the liposomes reduced the rate of peroxidation of the peroxidizable phospholipid acyl chains, possibly by restricting the length of chain reactions. The latter effect is believed to be caused by interference of the non-peroxidizable lipids in the bilayer. At low oxygen concentration lipid peroxidation was reduced. The cause of this limited peroxidation may be a reduced number of radical initiation reactions possibly involving oxygen-derived superoxide radicals. Killing of proliferating mammalian cells, irradiated at oxygen concentrations ranging from 0 to 100 per cent, appeared to be independent of the concentration of peroxidizable phospholipids in the cell membranes. This indicates that lipid peroxidation is not the determining process in radiation-induced reproductive cell death.

Limiting oxygen concentration

Membrane Lipids

10.1080/09553008414552151

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Citations (29)

Characterization of oxygen-tolerant Chinese hamster ovary cells

Free Radical Biology and Medicine (1988)

P. van der Valk Gilles Thomas L.H.W. van der Plas J. F. Jongkind Annemieke J.M.H. Verkerk

Energy charge

Oligomycin

10.1016/0891-5849(88)90086-x

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Citations (30)

Regional differences in radiosensitivity across the rat cervical spinal cord

International Journal of Radiation Oncology*Biology*Physics (2005)

Hendrik P. Bijl Peter van Luijk Robert P. Coppes Jacobus Maarten Schippers Antonius W.T. Konings

Penumbra

Radiosensitivity

10.1016/j.ijrobp.2004.10.018

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Citations (70)

Radiation-induced Structural Changes in Membrane Proteins of Human Erythrocytes and Ghosts and the Relation to Cellular Morphology

International Journal of Radiation Biology and Related Studies in Physics Chemistry and Medicine (1984)

Gerrit Jan Schuurhuis J Hommes Jan P. Vos I. Quintus Molenaar Antonius W.T. Konings

SummaryIsolated human erythrocytes and ghosts were irradiated with X-rays under different experimental conditions. The effect of the radiation treatment was examined with regard to the structure of membrane proteins as well as to the morphology of whole cells and ghosts. From sodium dodecyl sulphate/polyacrylamide gel electrophoresis it is concluded that spectrin (band 1 and 2) is the most radiosensitive of the membrane proteins examined. X-irradiation of cells and ghosts induced covalent cross-linking of a small fraction of membrane proteins. In the protein aggregates thus formed spectrin was found to be the major component. Molecular disulphide (-SS-) bridges seemed to account for part of the cross-links observed. Some nondisulphide cross-links were also found, especially when ghosts were irradiated. Significant amounts of spectrin aggregates were formed during post-irradiation incubation at 37°C but not at 4°C. In the intact cell a transformation in shape from discocyte to echinocyte accompanied the process of post-irradiation spectrin aggregation. The characteristics of both processes, such as their reversibility with adenosine, point to a metabolic involvement. It is shown that there is no causal relationship between the two phenomena observed. The possible cause of the post-irradiation effects and the parallelism with similar processes in nonirradiated metabolically depleted cells is discussed.KeywordsX-rayhuman erythrocyteghostsspectrinmorphology

Morphology

10.1080/09553008414550181

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Citations (23)

Unexpected changes of rat cervical spinal cord tolerance caused by inhomogeneous dose distributions

International Journal of Radiation Oncology*Biology*Physics (2003)

Hendrik P. Bijl Peter van Luijk Robert P. Coppes Jacobus Maarten Schippers Antonius W.T. Konings

10.1016/s0360-3016(03)00529-7

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Citations (111)

Impact Mechanisms of Ozone at Cell Level

Studies in environmental science (1989)

Ivonne M.C.M. Rietjens L. van Bree Antonius W.T. Konings P.J.A. Rombout G.M. Alink

Detoxification

GPX4

Mechanism of Action

10.1016/s0166-1116(08)70616-2

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Citations (0)

315 Plasma TGF-B levels during radiotherapy with or without carboplatin predicts pneumonitis in stage III non-small cell lung cancer (NSCLC)

Lung Cancer (1997)

Harry J.M. Groen M. van Waarden Eelco Fokkema A.H.D. van der Leest Antonius W.T. Konings

Carboplatin

Radiation Pneumonitis

Pneumonitis

10.1016/s0169-5002(97)89696-1

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Citations (6)

Inhibition of Repair of X-Ray-Induced DNA Damage by Heat: The Role of Hyperthermic Inhibition of DNA Polymerase α Activity

Radiation Research (1987)

Harm H. Kampinga Antonius W.T. Konings

10.2307/3577079

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Citations (18)

Cytotoxicity of Artemisinin-Related Endoperoxides to Ehrlich Ascites Tumor Cells

Journal of Natural Products (1993)

Herman J. Woerdenbag Tamara A. Moskal Niesko Pras Theo M. Malingré Farouk S. El‐Feraly

A series of artemisinin-related endoperoxides was tested for cytotoxicity to Ehrlich ascites tumor (EAT) cells using the microculture tetrazolium (MTT) assay. Artemisinin [1] had an IC50 value of 29.8 microM. Derivatives of dihydroartemisinin [2], being developed as antimalarial drugs (artemether [3], arteether [4], sodium artesunate [5], artelinic acid [6], and sodium artelinate [7]), exhibited a somewhat more potent cytotoxicity. Their IC50 values ranged from 12.2 to 19.9 microM. The presence of an exocyclic methylene fused to the lactone ring, as for artemisitene [9], led to higher cytotoxicity than 1. From the two epimeric 11-hydroxyartemisinin derivatives, the R form 12 showed a considerably higher cytotoxicity than the S form 13. Opening of the lactone ring of 1 dramatically reduced the cytotoxicity. The ether dimer 8 of 2 was the most potent cytotoxic agent, its IC50 being 1.4 microM. The variations in cytotoxicity between the structurally related compounds mostly correlated well with the theoretical capacity of radical formation and stabilization. In some cases lipophilicity or the presence of an electrophilic moiety seemed to have a determinant influence on cytotoxicity. The artemisinin-related endoperoxides showed cytotoxicity to EAT cells at higher concentrations than those needed for in vitro antimalarial activity, as reported in the literature.

Ehrlich ascites

10.1021/np50096a007

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Citations (276)