title: Exposure to benzidine caused apoptosis and malformation of telencephalon region in zebrafish.
abstract: Exposure to benzidine has been known to induce human cancers, particularly bladder carcinomas. In this study, the zebrafish model was used to investigate the developmental toxicity of benzidine. Embryos at 6 h postfertilization (hpf) that were exposed to benzidine exhibited embryonic death in a dose- and time-dependent manner. Benzidine induced malformations in zebrafish, such as small brain development, shorter axes, and a slight pericardial edema. High concentrations (50, 100, and 200 µM) of benzidine triggered widespread apoptosis in the brain and dorsal neurons, as evidenced by acridine orange and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assays. Real-time polymerase chain reaction analysis also showed that benzidine treatment affected p53, bax, and noxa expression. Decreases in specific brain markers, such as emx1 in the telencephalon, ngn1 in differentiated neurons, and otx2 in the midbrain, were observed in benzidine-treated embryos at 24 hpf. Conversely, no overt changes to pax2.1 expression in the midbrain-hindbrain boundary were found. Moreover, the use of Tg(HuC:GFP) zebrafish showed that benzidine caused a malformation of the telencephalon region. Our findings show that benzidine exposure triggers widespread apoptosis in the zebrafish brain and dorsal neurons, resulting in the development of an abnormal telencephalon.
authors.affiliation: Department of Biotechnology, Hungkuang University, Taichung, 43302, Taiwan.
authors.forename: Mark Hung-Chih
authors.initials: MH
authors.lastname: Chen
authors.forename: Li-Chi
authors.initials: LC
authors.lastname: Hsu
authors.forename: Jia-Lun
authors.initials: JL
authors.lastname: Wu
authors.forename: Chi-Wei
authors.initials: CW
authors.lastname: Yeh
authors.forename: Jen-Ning
authors.initials: JN
authors.lastname: Tsai
authors.forename: You-Cheng
authors.initials: YC
authors.lastname: Hseu
authors.forename: Li-Sung
authors.initials: LS
authors.lastname: Hsu
mesh_terms: D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001560:Benzidines / Q000633:toxicity*; D009474:Neurons / Q000378:metabolism; D013687:Telencephalon / Q000002:abnormalities* / Q000187:drug effects / Q000196:embryology; D015027:Zebrafish / Q000196:embryology
chemical_list: D051017:Apoptosis Regulatory Proteins; D001560:Benzidines; C029876:benzidine
keywords: apoptosis; benzidine; brain; zebrafish