DNA damage kinetics and apoptosis in ivermectin-treated chinese hamster ovary cells
Article first published online: 7 SEP 2012
Copyright © 2012 John Wiley & Sons, Ltd.
Journal of Applied Toxicology
Volume 33, Issue 11, pages 1260–1267, November 2013
How to Cite
Molinari, G., Kujawski, M., Scuto, A., Soloneski, S. and Larramendy, M. L. (2013), DNA damage kinetics and apoptosis in ivermectin-treated chinese hamster ovary cells. J. Appl. Toxicol., 33: 1260–1267. doi: 10.1002/jat.2782
- Issue published online: 20 SEP 2013
- Article first published online: 7 SEP 2012
- Manuscript Accepted: 10 MAY 2012
- Manuscript Revised: 12 APR 2012
- Manuscript Received: 12 MAR 2012
- CHO-K1 cells;
- comet assay;
- flow cytometry;
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. Copyright © 2012 John Wiley & Sons, Ltd.