Ethylnitrosourea induces neoplasia in zebrafish (Danio rerio)

Lee G. Beckwith, Jessica L. Moore, Gladys S. Tsao-Wu, John C. Harshbarger, Keith C. Cheng

Research output: Contribution to journalArticlepeer-review

82 Scopus citations


The zebrafish (Danio rerio) has been successfully used to discover hundreds of genes involved in development and organogenesis. To address the potential of zebrafish as a cancer model, it is important to determine the susceptibility of zebrafish to tumors. Germ line mutations are most commonly induced for zebrafish mutant screens by exposing adult male zebrafish to the alkylating agent, ethylnitrosourea (ENU). To determine whether ENU induces tumors, we compared the incidence of tumors in ENU-treated fish with untreated controls. Interestingly, 18 of 18 (100%) fish mutagenized with either 2.5 or 3.0 mM ENU developed epidermal papillomas, which numbered 1 to 22 per fish, within 1 year of treatment. The induced epidermal lesions included epidermal hyperplasia, flat papillomas (0.2 to 1.2 mm), and pedunculated papillomas (1.2 to 8 mm in greatest dimension), but no skin cancers. Angiogenesis was evident in papillomas larger than approximately 1 mm. All but two papillomas contained the three cell types (keratinocytes, club, and mucous cells) of normal zebrafish epidermis; histologic variants lacked either club cells or mucous cells. Two cavernous hemangiomas and a single malignant peripheral nerve sheath tumor were also found in the treated fish. None of five untreated controls developed tumors. These studies establish the feasibility of the zebrafish as an experimental model for the study of skin tumors.

Original languageEnglish (US)
Pages (from-to)379-385
Number of pages7
JournalLaboratory Investigation
Issue number3
StatePublished - Mar 2000

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine
  • Molecular Biology
  • Cell Biology


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