title: Evaluation of drug toxicity profiles based on the phenotypes of ascidian Ciona intestinalis.
abstract: In vivo toxicity evaluation using model organisms is an important step for the development of new drugs. Here, we report that Ciona intestinalis, a chordate invertebrate, is beneficial to drug toxicity evaluation for the following reasons: rapid embryonic and larval development, resemblance to vertebrates, ease of management, low cost, transparent body, and low risk of ethical issues. The dynamic phenotypic change of Ciona larvae during metamorphosis prompted us to examine the effect of cytotoxic drugs on its development by quantifying six toxicity endpoints: degenerated tail size, ampulla length, rotation of body axis, stomach size, heart rate, and body size. As a result, mitochondrial respiratory inhibitors, tubulin polymerization/depolymerization inhibitors, or DNA/RNA synthesis inhibitors showed distinct toxicity profiles against these six endpoints, but drugs with the same targets showed a similar toxicity profile in Ciona. Our results suggest Ciona is an effective animal model for profiling drug toxicity and exploring the mechanisms of drugs with unknown targets.
authors.affiliation: Department of Biosciences and Informatics, Faculty of Science and Technology, Keio University, Yokohama, Kanagawa 223-8522, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Mizotani
authors.affiliation: Department of Biosciences and Informatics, Faculty of Science and Technology, Keio University, Yokohama, Kanagawa 223-8522, Japan.
authors.forename: Shun
authors.initials: S
authors.lastname: Itoh
authors.affiliation: Department of Biosciences and Informatics, Faculty of Science and Technology, Keio University, Yokohama, Kanagawa 223-8522, Japan.
authors.forename: Kohji
authors.initials: K
authors.lastname: Hotta
authors.affiliation: Department of Biosciences and Informatics, Faculty of Science and Technology, Keio University, Yokohama, Kanagawa 223-8522, Japan.
authors.forename: Etsu
authors.initials: E
authors.lastname: Tashiro
authors.affiliation: Department of Biosciences and Informatics, Faculty of Science and Technology, Keio University, Yokohama, Kanagawa 223-8522, Japan.
authors.forename: Kotaro
authors.initials: K
authors.lastname: Oka
authors.affiliation: Department of Biosciences and Informatics, Faculty of Science and Technology, Keio University, Yokohama, Kanagawa 223-8522, Japan. Electronic address: imoto@bio.keio.ac.jp.
authors.forename: Masaya
authors.initials: M
authors.lastname: Imoto
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity; D002938:Ciona intestinalis / Q000187:drug effects*; D016000:Cluster Analysis; D018675:Toxicity Tests / Q000379:methods*
chemical_list: D000970:Antineoplastic Agents
keywords: Ciona intestinalis; DNA/RNA synthesis inhibitor; Mitochondria respiratory inhibitor; Toxicity endpoint; Toxicity profile; Tubulin polymerization/depolymerization inhibitor