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DNA damage kinetics and apoptosis in ivermectin‐treated chinese hamster ovary cells
Author(s) -
Molinari Gabriela,
Kujawski Maciej,
Scuto Anna,
Soloneski Sonia,
Larramendy Marcelo L.
Publication year - 2013
Publication title -
journal of applied toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.784
H-Index - 87
eISSN - 1099-1263
pISSN - 0260-437X
DOI - 10.1002/jat.2782
Subject(s) - chinese hamster ovary cell , microbiology and biotechnology , incubation , dna damage , comet assay , apoptosis , flow cytometry , hamster , cytotoxicity , dna , biology , cell , chemistry , andrology , in vitro , cell culture , biochemistry , genetics , medicine
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.