DNA damage kinetics and apoptosis in ivermectin‐treated chinese hamster ovary cells. Issue 11 (7th September 2012)

• Record Type: Journal Article
• Authors: Molinari, Gabriela; Kujawski, Maciej; Scuto, Anna; Soloneski, Sonia; Larramendy, Marcelo L.
• Is Part Of: Journal of applied toxicology. Volume 33:Issue 11(2013)
• Page Start: 1260
• Page End: 1267
• Publication Date: 2012-09-07
• Subjects: CHO‐K1 cells -- comet assay -- flow cytometry -- apoptosis -- ivermectin -- Ivomec®; Toxicology -- Periodicals; Industrial toxicology -- Periodicals; Environmentally induced diseases -- Periodicals; Toxicology -- Periodicals; 615.9005
• DOI: 10.1002/jat.2782
• Languages: English
• ISSNs: 0260-437X

Abstract

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. Copyright © 2012 John Wiley & Sons, Ltd. Abstract : Ivermectin (IVM)‐ and Ivomec® (IVO)‐induced DNA damage kinetics was analyzed by SCGE in CHO‐K1 treated with 50 µg ml –1 for 80 min. Viability remained unchanged up to 3 h. Afterwards, survival decreased up to 79% at 6 h, remaining unchanged within 12‐24 h. An increase of induced damage was observed within 0‐3 h whereas a decrease was revealed during the final 18 h. Both compounds induced apoptosis. The decrease in DNA lesions is mostly related to cytotoxicity than repair.