title: Assessment of cytotoxicity, apoptosis and DNA damages in Colo320 colorectal cancer cells selected for oxaliplatin resistance.
abstract: Despite the notable efficacy of oxaliplatin in the treatment of colorectal cancers, the metastatic tumours ultimately become resistant to the drug. This study investigated whether the oxaliplatin-resistant cells display different behaviour to this drug versus the sensitive cells and if this difference may be further exploited into the clinical treatments improvement. In order to establish a stable cell line resistant to oxaliplatin, a human colorectal cancer cell line (Colo320) was exposed to increasing doses of the drug up to the clinically relevant plasma concentration. Four cell groups with different levels of chemoresistance were subjected to additional doses of oxaliplatin, and their cytotoxicity, apoptosis and DNA damage production were assessed. Cells selected for resistance to oxaliplatin reacted differently to the application of additional doses of the drug, displaying lower toxicity and cellular death and fewer DNA cross-links formation, in accordance with the extent of the oxaliplatin pretreatments. As the cross-links formation by oxaliplatin being the main cause for cytotoxicity of this drug and a correlation between cytotoxicity and clinical outcome being shown repeatedly, we consider that the evaluation of oxaliplatin-induced cytotoxicity, apoptosis and DNA damage could be a valuable tool to assess the tumour cells sensitivity and thus to predict the response to chemotherapy.
authors.affiliation: Laboratory of Radiobiology and Tumor Biology, Chiricuta Cancer Institute, Cluj-Napoca, Romania. vpiroska@yahoo.com.
authors.forename: Piroska
authors.initials: P
authors.lastname: Virag
authors.forename: Ioana
authors.initials: I
authors.lastname: Brie
authors.forename: Eva
authors.initials: E
authors.lastname: Fischer-Fodor
authors.forename: Maria
authors.initials: M
authors.lastname: Perde-Schrepler
authors.forename: Corina
authors.initials: C
authors.lastname: Tatomir
authors.forename: Ovidiu
authors.initials: O
authors.lastname: Balacescu
authors.forename: Alexandru
authors.initials: A
authors.lastname: Irimie
authors.forename: Ion Dan
authors.initials: ID
authors.lastname: Postescu
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D003603:Cytotoxins / Q000494:pharmacology; D004249:DNA Damage; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D006801:Humans; D020128:Inhibitory Concentration 50; D009152:Mutagenicity Tests; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000494:pharmacology*; D000077150:Oxaliplatin
chemical_list: D000970:Antineoplastic Agents; D003603:Cytotoxins; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin