RRC ID 72252
著者 Kamata S, Hashiyama R, Hana-Ika H, Ohkubo I, Saito R, Honda A, Anan Y, Akahoshi N, Noguchi K, Kanda Y, Ishii I.
タイトル Cytotoxicity comparison of 35 developmental neurotoxicants in human induced pluripotent stem cells (iPSC), iPSC-derived neural progenitor cells, and transformed cell lines.
ジャーナル Toxicol In Vitro
Abstract The Organization for Economic Co-operation and Development (OECD) test guideline 426 for developmental neurotoxicity (DNT) of industrial/environmental chemicals depends primarily on animal experimentation. This requirement raises various critical issues, such as high cost, long duration, the sacrifice of large numbers of animals, and interspecies differences. This study demonstrates an alternative protocol that is simple, quick, less expensive, and standardized to evaluate DNT of many chemicals using human induced pluripotent stem cells (iPSC) and their differentiation to neural progenitor cells (NPC). Initially, concentration-dependent cytotoxicity of 35 DNT chemicals, including industrial materials, insecticides, and clinical drugs, were compared among iPSC, NPC, and two transformed cells, Cos-7 and HepG2, using tetrazolium dye (MTS)-reducing colorimetric and ATP luciferase assays, and IC50 values were calculated. Next, inhibitory effects of the 14 representative chemicals (mainly insecticides) on iPSC differentiation to NPC were evaluated by measuring altered expression of neural differentiation and undifferentiation marker genes. Results show that both iPSC and NPC were much more sensitive to most DNT chemicals than the transformed cells, and 14 chemicals induced differential patterns of marker gene expression, highlighting the validity and utility of the protocol for evaluation and classification of DNT chemicals and preclinical DNT tests for safety assessment.
巻・号 69
ページ 104999
公開日 2020-12-1
DOI 10.1016/j.tiv.2020.104999
PII S0887-2333(20)30549-X
PMID 32949729
MeSH Animals Cell Differentiation Cell Line Cell Survival Chlorocebus aethiops Drug Evaluation, Preclinical / methods Humans Induced Pluripotent Stem Cells / cytology Insecticides / toxicity Neural Stem Cells / cytology Neurotoxicity Syndromes* Toxicity Tests / methods*
IF 2.959
リソース情報
ヒト・動物細胞 COS-7(RCB0539) Hep G2(RCB1648)