ZFIN ID: ZDB-PUB-000411-1
Ethylnitrosourea induces neoplasia in zebrafish (Danio rerio)
Beckwith, L.G., Moore, J.L., Tsao-Wu, G.S., Harshbarger, J.C., and Cheng, K.C.
Date: 2000
Source: Laboratory investigation; a journal of technical methods and pathology   80(3): 379-385 (Journal)
Registered Authors: Beckwith, Lee G., Cheng, Keith C., Moore, Jessica L., Tsao-Wu, Gladys
Keywords: none
MeSH Terms:
  • Animals
  • Carcinogens/toxicity*
  • Ethylnitrosourea/toxicity*
  • Germ-Line Mutation
  • Male
  • Mutagens/toxicity
  • Neovascularization, Pathologic
  • Papilloma/blood supply
  • Papilloma/chemically induced*
  • Papilloma/genetics
  • Skin Neoplasms/blood supply
  • Skin Neoplasms/chemically induced*
  • Skin Neoplasms/genetics
  • Zebrafish
PubMed: 10744073 Full text @ Lab Invest.
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.