title: Toxicological evaluation of the topoisomerase inhibitor, etoposide, in the model animal Caenorhabditis elegans and 3T3-L1 normal murine cells.
abstract: Etoposide, a topoisomerase II inhibitor, has been widely used as a clinical anticancer drug to treat diverse cancer patients. Since not only rapidly dividing cancer cells but also the cells of normal human tissues and every living organism in environmental ecosystems have topoisomerases, it is crucial to study the toxicity of etoposide in other organisms in addition to cancer cells. In this study, we evaluated the toxicity of etoposide in both a soil nematode, Caenorhabditis elegans, and 3T3-L1 normal murine cells. Etoposide significantly retarded the growth, egg laying, and hatching in C. elegans. Etoposide also affected the reproductive gonad tissue, decreased the number of germ cells and induced abnormally enlarged nuclei in C. elegans. In addition, etoposide inhibited 3T3-L1 cell proliferation, with IC50values of 37.8 ± 7.3 and 9.8 ± 1.8 μM after 24 and 48 hours of treatment, respectively, via the induction of cell cycle arrest at the G2/M phase and apoptotic cell death. Etoposide also induced nuclear enlargement in 3T3-L1 normal murine cells. The reproductive toxicity and abnormal nuclear morphological changes seemed to correlate with the adverse effects of etoposide. We suggest that these experimental platforms, i.e., the toxicological evaluation of both nematodes and 3T3-L1 cells, may be useful to study the mechanisms underlying the side effects of chemicals, including topoisomerase inhibitors.
authors.affiliation: Systems Biotechnology Research Center, Korea Institute of Science and Technology, Gangneung, 25451, Korea.
authors.forename: So Young
authors.initials: SY
authors.lastname: Lee
authors.affiliation: Systems Biotechnology Research Center, Korea Institute of Science and Technology, Gangneung, 25451, Korea.
authors.forename: Joo Yeon
authors.initials: JY
authors.lastname: Kim
authors.affiliation: Systems Biotechnology Research Center, Korea Institute of Science and Technology, Gangneung, 25451, Korea.
authors.forename: Yu-Jin
authors.initials: YJ
authors.lastname: Jung
authors.affiliation: Systems Biotechnology Research Center, Korea Institute of Science and Technology, Gangneung, 25451, Korea.|Department of Biological Chemistry, University of Science and Technology (UST), Dajeon, 34113, Korea.
authors.forename: Kyungsu
authors.identifier: http://orcid.org/0000-0003-3846-7936
authors.initials: K
authors.lastname: Kang
mesh_terms: D041721:3T3-L1 Cells; D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects; D017173:Caenorhabditis elegans / Q000187:drug effects*; D018929:Cell Culture Techniques; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D002467:Cell Nucleus / Q000187:drug effects* / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D005047:Etoposide / Q000633:toxicity*; D006801:Humans; D051379:Mice; D008856:Microscopy, Fluorescence; D012098:Reproduction / Q000187:drug effects; D059005:Topoisomerase II Inhibitors / Q000633:toxicity*
chemical_list: D000970:Antineoplastic Agents; D059005:Topoisomerase II Inhibitors; D005047:Etoposide
keywords: 3T3-L1 cells; C. elegans; abnormal nuclei; cellular toxicity; etoposide; germ cell toxicity; reproductive toxicity; topoisomerase inhibitor