0000000000403895

AUTHOR

Rudolf Thust

showing 5 related works from this author

Apoptosis induced by (E)-5-(2-bromovinyl)-2'-deoxyuridine in varicella zoster virus thymidine kinase-expressing cells is driven by activation of c-Ju…

2003

The molecular mode of cell killing by the antiviral drug (E)-5-(2-bromovinyl-2'-deoxyuridine (BVDU) was studied in Chinese hamster ovary (CHO) cells stably transfected with the thymidine kinase gene (tk) of varicella zoster virus (CHO-VZVtk). The colony-forming ability of the cells was reduced to <1% at a concentration of approximately 1 microM BVDU, whereas for nontransfected cells or cells transfected with tk gene of herpes simplex virus type 1 (CHO-HSVtk), a 1000-fold higher dose was required to achieve the same response. BVDU inhibited thymidylate synthase in CHO-VZVtk but not in CHO-HSVtk and control cells. On the other hand, the drug was incorporated into DNA of VZVtk- and HSVtk-expre…

Herpesvirus 3 HumanFas Ligand ProteinFas-Associated Death Domain ProteinApoptosisCHO CellsBiologyTransfectionAntiviral AgentsThymidine KinaseFas ligandchemistry.chemical_compoundNecrosisCricetinaeCytotoxic T cellAnimalsSimplexvirusAdaptor Proteins Signal TransducingPharmacologyCaspase 8GenomeMembrane GlycoproteinsChinese hamster ovary cellCell CycleJNK Mitogen-Activated Protein KinasesTransfectionDNAThymidylate SynthaseMolecular biologyCaspase 9Transcription Factor AP-1Cell killingchemistryBromodeoxyuridineApoptosisThymidine kinaseCaspasesMolecular MedicineMitogen-Activated Protein KinasesCarrier ProteinsBromodeoxyuridineMolecular pharmacology
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Comparison of the genotoxic and apoptosis-inducing properties of ganciclovir and penciclovir in Chinese hamster ovary cells transfected with the thym…

2000

We studied the genotoxic and apoptosis-inducing properties of ganciclovir (GCV) and penciclovir (PCV) using Chinese hamster ovary cells stably transfected with the thymidine kinase (tk) gene of herpes simplex virus-1 (HSV-1). Cells expressing HSVtk were 300 and 100 times more sensitive than their isogenic HSVtk- counterparts to the cytotoxic effects of GCV and PCV, respectively. Using radiolabeled drugs, GCV was found to be incorporated into the genomic DNA much more effectively than PCV. GCV was highly potent in inducing chromosomal aberrations compared with PCV, which provoked less sister chromatid exchanges and chromosomal changes using equimolar or equitoxic doses. For both agents, apop…

GanciclovirDNA ReplicationCancer ResearchGuaninevirusesAcyclovirApoptosisCHO CellsHerpesvirus 1 HumanBiologymedicine.disease_causeTransfectioncomplex mixturesThymidine KinaseNecrosisCricetinaemedicineAnimalsMolecular BiologyGanciclovirMutagenicity TestsChinese hamster ovary cellCell CycleDNAGenetic TherapySuicide geneCell cycleMolecular biologyCell killingThymidine kinasePenciclovirMolecular MedicineSister Chromatid ExchangeGenotoxicitymedicine.drugCancer gene therapy
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Ganciclovir-induced apoptosis in HSV-1 thymidine kinase expressing cells: critical role of DNA breaks, Bcl-2 decline and caspase-9 activation.

2002

Although ganciclovir (GCV) is most often used in suicide anticancer gene therapy, the mechanism of GCV-induced cell killing and apoptosis is not fully understood. We analysed the mechanism of apoptosis triggered by GCV using a model system of CHO cells stably transfected with HSV-1 thymidine kinase (HSVtk). GCV-induced apoptosis is due to incorporation of the drug into DNA resulting in replication-dependent formation of DNA double-strand breaks and, at later stages, S and G2/M arrest. GCV-provoked DNA instability was likely to be responsible for the observed initial decline in Bcl-2 level and caspase-9/-3 activation. Further decline in the Bcl-2 level was due to cleavage of the protein by c…

Cancer ResearchTime FactorsvirusesPoly ADP ribose polymeraseApoptosisCytochrome c GroupCHO CellsHerpesvirus 1 HumanTransfectionThymidine KinaseCricetinaeGeneticsAnimalsfas ReceptorMolecular BiologyGanciclovirbiologyReverse Transcriptase Polymerase Chain ReactionCytochrome cCell CycleTransfectionSuicide geneFas receptorMolecular biologyCaspase 9Enzyme ActivationGene Expression Regulation NeoplasticCell killingProto-Oncogene Proteins c-bcl-2ApoptosisThymidine kinaseCaspasesbiology.proteinPoly(ADP-ribose) PolymerasesDNA DamageOncogene
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Comparative analysis of DNA breakage, chromosomal aberrations and apoptosis induced by the anti-herpes purine nucleoside analogues aciclovir, gancicl…

2002

Nucleoside analogues have been used in antiviral therapy and suicide cancer gene therapy. Therefore, it is of importance to compare their potential cytotoxic and genotoxic action. Using metabolically competent CHO cells expressing the thymidine kinase gene of herpes simplex virus type 1 (CHO-HSVtk cells) as a model system, the induction of DNA breaks was compared with the induction of structural chromosomal aberrations and apoptosis/necrosis after exposure to the anti-herpes nucleoside analogues aciclovir (ACV), ganciclovir (GCV) and penciclovir (PCV). After continuous treatment of CHO-HSVtk cells with the drugs, LD(10) in a colony-forming assay was 50, 0.5 and 1 microM for ACV, GCV and PCV…

GanciclovirGuanineDNA damagevirusesHealth Toxicology and MutagenesisAcyclovirApoptosisCHO CellsBiologymedicine.disease_causeAntiviral AgentsThymidine KinaseChromosomesColony-Forming Units AssayNecrosisCricetulusCricetinaeGeneticsmedicineCytotoxic T cellAnimalsSimplexvirusAciclovirEnzyme InhibitorsMolecular BiologyGanciclovirChromosome AberrationsDNAMolecular biologyHerpes simplex virusApoptosisPenciclovirNucleosidemedicine.drugDNA DamageMutation research
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Protective effect of O6-methylguanine-DNA methyltransferase (MGMT) on the cytotoxic and recombinogenic activity of different antineoplastic drugs

1996

The DNA repair protein O6-methylguanine-DNA methyltransferase (MGMT) removes alkyl groups from the O6 position of guanine in DNA and thus may protect cells against genotoxic effects of agents inducing this lesion. To analyze quantitatively the level of protection mediated by MGMT against antineoplastic drugs, we determined the cytotoxic and recombinogenic (sister-chromatid exchange inducing) effects of various chemotherapeutic agents in a pair of isogenic Chinese hamster cell lines deficient and proficient for MGMT, generated upon transfection with human MGMT cDNA. Furthermore, we compared the responses of the human cell lines HeLa MR (MGMT deficient) and HeLa S3 (MGMT proficient) to the va…

MelphalanCancer ResearchMethyltransferaseCell SurvivalAntineoplastic AgentsCHO CellsDNA methyltransferaseHeLaO(6)-Methylguanine-DNA Methyltransferasechemistry.chemical_compoundMafosfamideCricetinaemedicineAnimalsCytotoxic T cellneoplasmsCisplatinGeneticsbiologyChlorambucilMethyltransferasesbiology.organism_classificationdigestive system diseasesOncologychemistryCancer researchSister Chromatid Exchangemedicine.drugInternational Journal of Cancer
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