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Ethylnitrosourea induces neoplasia in zebrafish (Danio rerio)
L G Beckwith1, J L Moore, G S Tsao-Wu
1Jake Gittlen Cancer Research Institute, Department of Pathology, Pennsylvania State University College of Medicine, Hershey 17033, USA.
Abstract:
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.
Insights
Ethylnitrosourea (ENU) treatment induced skin tumors in 100% of zebrafish, establishing their utility as a cancer model. These findings highlight zebrafish
Area of Science:
- Developmental Biology
- Cancer Research
- Aquatic Toxicology
Background:
- Zebrafish (Danio rerio) are valuable for genetic studies.
- Understanding zebrafish tumor susceptibility is crucial for cancer modeling.
- Ethylnitrosourea (ENU) is a common mutagen for zebrafish germ line mutations.
Purpose of the Study:
- To evaluate zebrafish susceptibility to tumors induced by ENU.
- To establish the feasibility of zebrafish as a model for skin tumor research.
Main Methods:
- Adult male zebrafish were treated with ethylnitrosourea (ENU) at 2.5 or 3.0 mM.
- Tumor incidence in ENU-treated fish was compared to untreated controls.
- Histological analysis of induced lesions was performed.
Main Results:
- 100% of ENU-treated zebrafish (18/18) developed epidermal papillomas within one year.
- Induced lesions included hyperplasia and papillomas of varying sizes, but no skin cancers.
- Two cavernous hemangiomas and one malignant peripheral nerve sheath tumor were observed in treated fish; controls had no tumors.
Conclusions:
- Zebrafish are highly susceptible to ENU-induced skin tumors.
- The zebrafish is a feasible and effective model for studying skin tumors.
- Further research can leverage zebrafish for skin cancer research.