0000000000730341

AUTHOR

Kerstin Fabian

showing 2 related works from this author

Xrcc2 deficiency sensitizes cells to apoptosis by MNNG and the alkylating anticancer drugs temozolomide, fotemustine and mafosfamide

2006

DNA double-strand breaks (DSBs) are potent killing lesions, and inefficient repair of DSBs does not only lead to cell death but also to genomic instability and tumorigenesis. DSBs are repaired by non-homologous end-joining and homologous recombination (HR). A key player in HR is Xrcc2, a Rad51-like protein. Cells deficient in Xrcc2 are hypersensitive to X-rays and mitomycin C and display increased chromosomal aberration frequencies. In order to elucidate the role of Xrcc2 in resistance to anticancer drugs, we compared Xrcc2 knockout (Xrcc2-/-) mouse embryonic fibroblasts with the corresponding isogenic wild-type and Xrcc2 complemented knockout cells. We show that Xrcc2-/- cells are hypersen…

MethylnitronitrosoguanidineCancer ResearchProgrammed cell deathDNA repairDNA damageMitomycinApoptosisBiologyNitrosourea Compoundschemistry.chemical_compoundOrganophosphorus CompoundsMafosfamideTemozolomidemedicineHumansCytotoxic T cellAntineoplastic Agents AlkylatingCyclophosphamideCisplatinMolecular biologyDNA-Binding ProteinsDacarbazineOncologychemistryApoptosisFotemustineCisplatinMutagensmedicine.drugCancer Letters
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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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