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Effects of Cisplatin Chemotherapy Drug in Zebrafish
Author(s) -
De Jesus Hector Jose,
Podratz Jewel,
Greenwood Tammy M,
Ekker Stephen C,
Windebank Anthony J
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.943.7
Subject(s) - cisplatin , tunel assay , zebrafish , neurotoxicity , apoptosis , cancer research , carboplatin , terminal deoxynucleotidyl transferase , danio , pharmacology , chemotherapy , biology , toxicity , medicine , biochemistry , gene
Chemotherapy‐induced peripheral neuropathy is a serious, lifelong side effect that impairs quality of life for long‐term cancer survivors. Cisplatin (a platinum based chemotherapy drug) is used to treat various cancers. However, platinum drug‐induced neuropathy in 20–30 percent of patients and it is a dose‐limiting side effect. The chemotherapeutic mechanism of cisplatin is through DNA binding, inducing DNA damage leading to apoptosis. Our study used zebrafish (Danio rerio), that have a nervous system shown to be regulated by shared death pathways including p53, to establish a model of cisplatin neurotoxicity. We show a survival curve of 72 hour post fertilization zebrafish treated with cisplatin that was dose and time‐dependent. Immunostaining with terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) showed cisplatin induced cellular apoptosis. Moreover, to demonstrate if cisplatin causes neuron‐specific apoptosis we colocalized Elav antibody (neuron‐specific marker) with TUNEL assay. This new model of cisplatin neurotoxicity in zebrafish will allow further study of the p53 signaling pathway and its involvement in platinum drug‐induced neurotoxicity.