Search results for "Methyl Methanesulfonate"

showing 8 items of 18 documents

Ras-Related GTPase RhoB Forces Alkylation-Induced Apoptotic Cell Death

2000

rhoB encoding a Ras-related GTPase is immediate-early inducible by genotoxic treatments. To address the question of the physiological role of RhoB in cellular defense, cells stably overexpressing wild-type RhoB protein were generated. Overexpression of RhoB renders cells hypersensitive to the killing effect of alkylating agents including antineoplastic drugs but not to UV-light and doxorubicin. As compared to control cells, RhoB overexpressing cells revealed an increase in the frequency of alkylation-induced apoptotic cell death. This indicates that RhoB is involved in modulating apoptotic signaling. Furthermore, overexpression of RhoB resulted in a prolonged transient block to DNA replicat…

DNA ReplicationDNA ComplementaryAlkylationDNA RepairUltraviolet RaysRHOBBiophysicsApoptosisGTPaseBiologyTransfectionBiochemistryMicechemistry.chemical_compoundRhoB GTP-Binding ProteinmedicineAnimalsDoxorubicinrhoB GTP-Binding ProteinCytotoxicityAntineoplastic Agents AlkylatingMolecular BiologyDNA replication3T3 CellsCell BiologyMethyl MethanesulfonateRatsCell biologychemistryApoptosisCancer researchDNADNA Damagemedicine.drugBiochemical and Biophysical Research Communications
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Modulation of induced reversion frequency by nucleotide pool imbalance as a tool for mutant characterization.

1987

Addition of thymidine (TdR) or deoxycytidine (CdR) to the culture medium during posttreatment incubation affected the frequency of mutagen-induced reversion in three hypoxanthine-guanine phosphoribosyl transferase-deficient mutants of V79 Chinese hamster cells. With two of the mutants (E20 and I3), reversions induced by N-ethylnitrosourea, ethyl methanesulfonate, and methyl methanesulfonate were enhanced by TdR and were either decreased (E20) or not affected (I3) by CdR. With the third mutant (E21), alkylating agent-induced reversions were enhanced by CdR and decreased by TdR. Finally, 6-amino-2-hydroxypurine induced reversions were enhanced by TdR in mutant I3 and were decreased by TdR or …

MaleEthyl methanesulfonateEpidemiologyHealth Toxicology and MutagenesisMutantReversionMutagenesis (molecular biology technique)BiologyDeoxycytidineCell Linechemistry.chemical_compoundCricetulusDeoxyadenosineCricetinaeAnimalsGenetics (clinical)DeoxyadenosinesNucleotidesPoint mutationFibroblastsMethyl methanesulfonatechemistryBiochemistryMutationThymidineMutagensThymidineEnvironmental and molecular mutagenesis
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Apaf-1 deficient mouse fibroblasts are resistant to MNNG and MMS-induced apoptotic death without attenuation of Bcl-2 decline.

2005

Abstract Simple alkylating agents induce cell death by activating the apoptotic pathway. In rodent fibroblasts, apoptosis triggered by DNA methylation lesions is executed via the mitochondrial damage pathway. Here, we studied cell death induced by the methylating agents methyl methanesulfonate (MMS) and N-methyl-N′-nitro-N-nitrosoguanidine (MNNG) in mouse fibroblasts wild-type (wt) and deficient for Apaf-1 (apaf-1 knockout cells). Apaf-1 is an essential component of the apoptosome complex that becomes activated upon cytochrome c release from mitochondria. We show that apaf-1 knockout cells are more resistant to the cytotoxic effect (as measured by WST assay) of methylating agents. This is d…

PharmacologyProgrammed cell deathMethylnitronitrosoguanidineDNA damageCytochrome cApoptosisBiologyToxicologyMethyl MethanesulfonateMolecular biologyMethyl methanesulfonatechemistry.chemical_compoundMiceApoptotic Protease-Activating Factor 1chemistryProto-Oncogene Proteins c-bcl-2Cell cultureApoptosisbiology.proteinCytotoxic T cellAnimalsApoptosomeCell Line TransformedToxicology and applied pharmacology
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Effect of ultraviolet light, methyl methanesulfonate and ionizing radiation on the genotoxic response and apoptosis of mouse fibroblasts lacking c-Fo…

2001

c-Fos and p53 are DNA damage-inducible proteins that are involved in gene regulation, cell cycle checkpoint control and cell proliferation following exposure to genotoxic agents. To investigate comparatively the role of c-Fos and p53 in the maintenance of genomic stability and the induction of apoptosis, we generated mouse fibroblast cell lines from knockout mice deficient for either c-fos (fos -/-) or p53 (p53-/-) or for both gene products (fosp53-/-). The sensitivity of these established cell lines was compared with the corresponding wild-type cells as to the cytotoxic, clastogenic and apoptosis-inducing effects of ultraviolet (UV-C) light and methyl methanesulfonate (MMS). Additionally, …

Programmed cell deathTime FactorsCell cycle checkpointCell SurvivalUltraviolet RaysHealth Toxicology and MutagenesisBlotting WesternApoptosisBiologyToxicologyPolymerase Chain ReactionCell LineMiceNecrosischemistry.chemical_compoundRadiation IonizingGeneticsUltraviolet lightAnimalsCytotoxic T cellCells CulturedGenetics (clinical)Chromosome AberrationsMice KnockoutCell growthDose-Response Relationship RadiationFibroblastsBlotting NorthernMethyl MethanesulfonateMolecular biologyMethyl methanesulfonatechemistryApoptosisCell cultureTumor Suppressor Protein p53Proto-Oncogene Proteins c-fosDNA DamageMutagensMutagenesis
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Is the repair of oxidative DNA base modifications inducible by a preceding DNA damage induction?

2007

In mammalian cells, 7,8-dihydro-8-oxoguanine (8-oxoG) and some other oxidative guanine modifications are removed from the DNA by base excision repair, which is initiated by OGG1 protein. We have tested whether this repair is inducible in mouse embryonic fibroblasts (MEFs), MCF-7 breast cancer cells and primary human fibroblasts by a pretreatment with the photosensitizer Ro19-8022 plus light, which generates predominantly 8-oxoG, or with methyl methanesulfonate (MMS), which generates alkylated bases and abasic sites (AP sites). The results indicate that the repair rate of the oxidative guanine modifications induced by the photosensitizer was not increased if a priming dose of the oxidative o…

PyrrolidinesTime FactorsDNA RepairDNA repairGuanineDNA damageBiologymedicine.disease_causeBiochemistryMicechemistry.chemical_compoundTumor Cells CulturedmedicineAnimalsHumansheterocyclic compoundsAntineoplastic Agents AlkylatingBase PairingMolecular BiologyPhotosensitizing AgentsGuanosineDNACell BiologyBase excision repairGlutathioneFibroblastsMethyl MethanesulfonateGlutathioneMolecular biologyMethyl methanesulfonateOxidative StresschemistryFemaleOxidation-ReductionQuinolizinesDNAOxidative stressDNA DamageDNA Repair
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Expression of yeast but not human apurinic/apyrimidinic endonuclease renders Chinese hamster cells more resistant to DNA damaging agents.

1997

Abasic sites represent ubiquitous DNA lesions that arise spontaneously or are induced by DNA-damaging agents. They block DNA replication and are considered to be cytotoxic and mutagenic. The key enzymes involved in the repair of abasic sites are apurinic/apyrimidinic (AP) endonucleases which process these lesions in an error-free mechanism. To analyze the role of AP endonuclease in the protection of mammalian cells against DNA damaging agents, we have transfected both the human (APE) and the yeast (APN1) AP endonuclease in Chinese hamster cells and compared the effects of expression of these genes in stable transfectants as to survival of cells and formation of chromosomal aberrations. Alth…

Saccharomyces cerevisiae ProteinsDNA RepairDNA repairCell SurvivalBlotting WesternCarbon-Oxygen LyasesChromosome DisordersCHO CellsToxicologyTransfectionAP endonucleaseDNA repair ; Apurinic endonuclease ; cellular defense mechanismschemistry.chemical_compoundCricetinaeGeneticsDNA-(Apurinic or Apyrimidinic Site) LyaseAnimalsHumansAP siteRNA MessengerFluorescent Antibody Technique IndirectMolecular BiologyCell NucleusChromosome AberrationsEndodeoxyribonucleasesbiologyCell DeathfungiNuclear ProteinsBase excision repairHydrogen PeroxideBlotting NorthernMethyl MethanesulfonateMolecular biologyDNA-(apurinic or apyrimidinic site) lyaseDNA Repair EnzymeschemistryGene Expression Regulationbiology.proteinChromosome breakageDNANucleotide excision repairDNA DamagePlasmidsMutation research
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Transcriptional activation of the small GTPase gene rhoB by genotoxic stress is regulated via a CCAAT element

2001

The gene encoding the Ras-related GTPase RhoB-specific is immediate-early inducible by genotoxic treatments. Regulation of transcriptional activation of rhoB is still unclear. Here we show that cells lacking either p53 or c-Fos are not different from wild-type cells with respect to the level of rhoB induction upon UV irradiation, indicating that these transcription factors are not crucial for stimulation of rhoB mRNA expression. Extracts from UV-irradiated and non-irradiated cells revealed similar DNA-binding activities to a 0.17 kb rhoB promoter fragment harboring the functional element(s) necessary for stimulation of rhoB by UV light. By means of immunoprecipitation we found that an ATF-2…

Transcriptional ActivationImmunoprecipitationUltraviolet RaysRHOBMolecular Sequence DataCAAT boxOligonucleotidesBiologyResponse ElementsArticlechemistry.chemical_compoundMiceRhoB GTP-Binding ProteinGeneticsAnimalsSmall GTPaseRNA MessengerPromoter Regions GeneticrhoB GTP-Binding ProteinTranscription factorBinding SitesCcaat-enhancer-binding proteinsBase Sequence3T3 CellsDNAMolecular biologyMethyl methanesulfonatechemistryCCAAT-Binding FactorMutationCCAAT-Enhancer-Binding ProteinsProtein BindingTranscription Factors
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Inhibition of Protein Isoprenylation Impairs Rho-Regulated Early Cellular Response to Genotoxic Stress

2000

Activation of c-Jun N-terminal kinases (JNKs) and nuclear factor-kappaB (NF-kappaB) are early cellular responses to genotoxic stress involved in the regulation of gene expression. Pretreatment of cells with the hydroxymethyl glutaryl-CoA reductase inhibitor lovastatin blocked stimulation of JNK1 activity by UV irradiation and by treatment with the alkylating compound methyl methanesulfonate but did not affect activation of extracellular signal-regulated kinase 2 by UV light. Lovastatin also attenuated UV-induced degradation of the NF-kappaB inhibitor IkappaBalpha. The effects of lovastatin on UV-triggered stimulation of JNK1 as well as on IkappaBalpha degradation were reverted by cotreatmen…

rho GTP-Binding ProteinsProtein PrenylationStimulationClostridium difficile toxin BCHO CellsGenotoxic StressBiologychemistry.chemical_compoundCricetinaemedicineAnimalsHumansMitogen-Activated Protein Kinase 8LovastatinPharmacologyMutagenicity TestsKinaseFarnesyltransferase inhibitorNF-kappa BMethyl methanesulfonateCell biologyIκBαchemistryMolecular MedicineLovastatinHydroxymethylglutaryl-CoA Reductase InhibitorsMitogen-Activated Protein KinasesHeLa CellsSignal Transductionmedicine.drugMolecular Pharmacology
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