title: Oxcarbazepine-induced cytotoxicity and genotoxicity in human lymphocyte cultures with or without metabolic activation.
abstract: There has been considerable debate about the relationship between epilepsy and cancer. Oxcarbazepine (OXC) is used for treating certain types of seizures in patients with epilepsy. There have been no detailed investigations about genotoxicity of OXC and its metabolites. Therefore, the aim of this study is to investigate the cytotoxic and genotoxic effects of OXC and its metabolites on cultured human lymphocytes. The cytotoxicity and genotoxicity of OXC on human peripheral blood lymphocytes were examined in vitro by sister chromatid exchange (SCE), chromosomal aberration (CA) and micronucleus (MN) tests. Cultures were treated with 125, 250 and 500 μg/ml of OXC in the presence (3 h treatment) and absence (24 h and 48 h treatment) of a metabolic activator (S9 mix). Dimethyl sulfoxide (DMSO) was used as a solvent control. OXC showed cytotoxic activities due to significant decreases in mitotic index (MI), proliferation index (PI) and nuclear division index (NDI) in the absence of S9 mix when compared with solvent control. Metabolites of OXC also significantly reduced MI and PI in cultures with S9 mix. OXC significantly increased the CAs, aberrant cells, SCE and MN values in the presence and absence of S9 mix. Our results indicated that both OXC and its metabolites have cytotoxic, cytostatic and genotoxic potential on human peripheral blood lymphocyte cultures under the experimental conditions. Further studies are necessary to elucidate the relationship between cytotoxic, cytostatic and genotoxic effects, and to make a possible risk assessment in patients receiving therapy with this drug.
authors.affiliation: a Department of Biology, Faculty of Science and Letters , Ordu University , Ordu , Turkey.
authors.forename: Zülal
authors.initials: Z
authors.lastname: Atlı Şekeroğlu
authors.affiliation: b Department of Biology, Faculty of Science and Letters , Ondokuz Mayıs University , Samsun , Turkey.
authors.forename: Haluk
authors.initials: H
authors.lastname: Kefelioğlu
authors.affiliation: a Department of Biology, Faculty of Science and Letters , Ordu University , Ordu , Turkey.
authors.forename: Seval
authors.initials: S
authors.lastname: Kontaş Yedier
authors.affiliation: a Department of Biology, Faculty of Science and Letters , Ordu University , Ordu , Turkey.
authors.forename: Vedat
authors.initials: V
authors.lastname: Şekeroğlu
authors.affiliation: b Department of Biology, Faculty of Science and Letters , Ondokuz Mayıs University , Samsun , Turkey.
authors.forename: Berrin
authors.initials: B
authors.lastname: Delmecioğlu
mesh_terms: D000328:Adult; D000927:Anticonvulsants / Q000378:metabolism / Q000633:toxicity*; D002220:Carbamazepine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000633:toxicity; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002869:Chromosome Aberrations / Q000139:chemically induced*; D004305:Dose-Response Relationship, Drug; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D048629:Micronuclei, Chromosome-Defective / Q000139:chemically induced; D008862:Microsomes, Liver / Q000378:metabolism; D009153:Mutagens / Q000378:metabolism / Q000633:toxicity*; D000078330:Oxcarbazepine; D012854:Sister Chromatid Exchange / Q000187:drug effects*; D055815:Young Adult
chemical_list: D000927:Anticonvulsants; D009153:Mutagens; D002220:Carbamazepine; D000078330:Oxcarbazepine
keywords: Oxcarbazepine; chromosome aberration; cytotoxicity; micronucleus; sister chromatid exchange