title: Cytotoxic and genotoxic effects of fumonisin B1 on rabbit kidney RK13 cell line.
abstract: Fumonisins, mycotoxins produced by certain strains of Fusarium moniliforme, could induce various diseases in animals and are suspected human carcinogens. Fumonisin B1 (FB1), the most commonly found fumonisin, has been characterised as a tumour initiator and a tumour promoter, a mitogen and an anti-proliferative agent. In this study we examined the cytotoxicity and genotoxicity of FB1 in rabbit kidney RK13 cells. To evaluate the effects of FB1 on survival of this cell line we analysed cell viability, membrane integrity, DNA fragmentation and overall morphology of the cells. The genotoxic potential of FB1 was estimated by monitoring the ability of this mycotoxin to induce micronuclei in RK13 cells. Exposure to FB1 caused a significant increase in micronucleus frequency in a concentration- and in a time-dependent manner. Nanomolar concentrations of FB1 decreased cell viability after 24 h and even more so after 48 h of exposure. The morphological changes observed suggested that an increased number of RK13 cells were dying by the process of apoptosis. However, FB1 also induced impairments of cell and mitochondrial membrane integrity, as assessed by lactate dehydrogenase and glutamate dehydrogenase leakage. These results could imply that nanomolar concentrations of FB1 induced apoptosis, which subsequently may proceed to secondary necrosis. In summary, our observations suggest that FB1 is genotoxic and cytotoxic to RK13 cells.
authors.affiliation: Department of Medical Biochemistry and Haematology, Faculty of Pharmacy and Biochemistry, University of Zagreb, Domagojeva 2, 10000 Zagreb, Croatia. lada.rumora@fbf.tel.hr
authors.forename: Lada
authors.initials: L
authors.lastname: Rumora
authors.forename: Sanja
authors.initials: S
authors.lastname: Kovacić
authors.forename: Ruzica
authors.initials: R
authors.lastname: Rozgaj
authors.forename: Ivana
authors.initials: I
authors.lastname: Cepelak
authors.forename: Stjepan
authors.initials: S
authors.lastname: Pepeljnjak
authors.forename: Tihana
authors.initials: T
authors.lastname: Zanić Grubisić
mesh_terms: D000818:Animals; D002264:Carboxylic Acids / Q000633:toxicity*; D002461:Cell Line, Transformed; D002470:Cell Survival / Q000187:drug effects; D004247:DNA / Q000187:drug effects; D053938:DNA Fragmentation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000187:drug effects / Q000473:pathology; D037341:Fumonisins; D007425:Intracellular Membranes / Q000187:drug effects; D007672:Kidney Cortex / Q000187:drug effects* / Q000473:pathology; D015162:Micronucleus Tests; D009153:Mutagens / Q000633:toxicity*; D011817:Rabbits
chemical_list: D002264:Carboxylic Acids; D037341:Fumonisins; D009153:Mutagens; C056933:fumonisin B1; D004247:DNA