title: DNA damage kinetics and apoptosis in ivermectin-treated Chinese hamster ovary cells.
abstract: A comet assay was used to analyze DNA damage kinetics in Chinese hamster ovary (CHO-K1) cells induced by antiparasitic ivermectin (IVM) and the IVM-containing technical formulation Ivomec® (IVO; 1% IVM). Cells were treated with 50 µg ml(-1) IVM and IVO for 80 min, washed and re-incubated in antiparasiticide-free medium for 0-24 h until assayed using the single-cell gel electrophoresis assay (SCGE). Cell viability remained unchanged up to 3 h of incubation. After 6 h of treatment, cell survival decreased up to 75% and 79% in IVM- and IVO-treated cultures, respectively, remaining unchanged within 12-24 h after treatment. For both anthelmintics, biphasic behavior in DNA damage occurred during the incubation time. A time-dependent increase of IVM- and IVO-induced DNA damage was observed within 0 to 3 h after pulse treatment, revealed by a progressive decrease of undamaged cells and an increase in slightly damaged and damaged cells. Finally, a time-dependent decrease in IVM- and IVO-induced DNA damage was revealed by a progressive decrease of slightly damaged cells and the absence of damaged cells simultaneously with an increase in the frequency of undamaged cells during the final 18 h of incubation. Flow cytometry analysis revealed that both compounds are able to induce a marked increase in early and late apoptosis. Based on our observations, we could conclude that the decrease in DNA lesions is mostly related to IVM-induced cytotoxicity rather than attributable to a repair process.
authors.affiliation: Cátedra de Citología, Facultad de Ciencias Naturales y Museo, Universidad Nacional de La Plata, Calle 64 Nº, 3 B1904AMA, La Plata, Argentina.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Molinari
authors.forename: Maciej
authors.initials: M
authors.lastname: Kujawski
authors.forename: Anna
authors.initials: A
authors.lastname: Scuto
authors.forename: Sonia
authors.initials: S
authors.lastname: Soloneski
authors.forename: Marcelo L
authors.initials: ML
authors.lastname: Larramendy
mesh_terms: D000818:Animals; D000871:Anthelmintics / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects*; D016466:CHO Cells; D018929:Cell Culture Techniques; D002470:Cell Survival / Q000187:drug effects; D020552:Comet Assay; D003412:Cricetulus; D004249:DNA Damage; D004260:DNA Repair; D005434:Flow Cytometry; D007559:Ivermectin / Q000633:toxicity*; D007700:Kinetics
chemical_list: D000871:Anthelmintics; D007559:Ivermectin