TY - JOUR
T1 - Ethylnitrosourea induces neoplasia in zebrafish (Danio rerio)
AU - Beckwith, Lee G.
AU - Moore, Jessica L.
AU - Tsao-Wu, Gladys S.
AU - Harshbarger, John C.
AU - Cheng, Keith C.
N1 - Funding Information:
Supported by National Institutes of Health Grants 5R01-CA73935 (KCC), 1F 32GM19794 (JLM), and NO1-CB-77021 (JCH); National Science Foundation Grant MCB-9604923 (KCC); and Jake Gittlen Memorial Golf Tournament. Address reprint requests to: Dr. K. C. Cheng, Jake Gittlen Cancer Research Institute, H059, Pennsylvania State University College of Medicine, 500 University Drive, Hershey, Pennsylvania 17033. Fax: (717) 531-5634; E-mail: [email protected]
PY - 2000/3
Y1 - 2000/3
N2 - 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.
AB - 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.
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U2 - 10.1038/labinvest.3780042
DO - 10.1038/labinvest.3780042
M3 - Article
C2 - 10744073
AN - SCOPUS:0034065501
SN - 0023-6837
VL - 80
SP - 379
EP - 385
JO - Laboratory Investigation
JF - Laboratory Investigation
IS - 3
ER -