title: Ara-C induces apoptosis in monkey fibroblast cells.
abstract: The effect of cytosine arabinoside (Ara-C) on cell viability has been studied in African green monkey kidney fibroblasts (CV1-P). It has been shown previously that Ara-C- induced cell death in neurons is mediated by apoptosis. We investigated whether Ara-C can induce apoptosis also in CV1-P cells, and if the apoptosis is p53-associated. For comparison, human neuroblastoma cells (SH-SY5Y) were studied as a model of human neuronal cells. SYTO13/propidium iodide staining revealed condensed and fragmented nuclei in both cell lines. Ara-C treatment for 48 h induced approximately 24% apoptosis in CV1-P cells whereas approximately 55% of SH-SY5Y cells were apoptotic. Ara-C increased the level of p53 in both CV1-P and SH-SY5Y cells compared to control. The maximum level of p53 in SH-SY5Y cells was reached at 12 h and this then rapidly faded whereas CV1-P cells p53 levels remained elevated after reaching their maximum. Caspase-3 activity was 5-fold higher in human neuroblastoma cells than in monkey fibroblasts, this reflected the decreased cell viability. Our results prove that Ara-C- induced apoptosis in CV1-P cells is associated with an increase of p53 and activation of caspase-3. Ara-C-induced toxicity in CV1-P cells is modest compared to that seen in neuronal cells.
authors.affiliation: Department of Pharmacology and Toxicology, University of Kuopio, PO Box 1627, FIN-70211, Kuopio, Finland. manakova@uku.fi
authors.forename: Sárka
authors.initials: S
authors.lastname: Mañáková
authors.forename: Katja A
authors.initials: KA
authors.lastname: Puttonen
authors.forename: Atso
authors.initials: A
authors.lastname: Raasmaja
authors.forename: Pekka T
authors.initials: PT
authors.lastname: Männistö
mesh_terms: D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects*; D018929:Cell Culture Techniques; D002522:Chlorocebus aethiops; D003561:Cytarabine / Q000633:toxicity*; D005347:Fibroblasts; D005786:Gene Expression Regulation; D007668:Kidney / Q000166:cytology; D009474:Neurons; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis / Q000494:pharmacology
chemical_list: D000964:Antimetabolites, Antineoplastic; D016159:Tumor Suppressor Protein p53; D003561:Cytarabine