Neoplasia and Neoplasm-Associated Lesions in Laboratory Colonies of Zebrafish Emphasizing Key Influences of Diet and Aquaculture System Design

Jan M. Spitsbergen, Donald R. Buhler, and Tracy S. Peterson

Jan Spitsbergen, DVM, PhD, DACVP, is a fish biologist, fish pathologist, and veterinary toxicologic pathologist in the Department of Microbiology; Donald Buhler, PhD, is a toxicologist and emeritus professor in the Department of Environmental and Molecular Toxicology; and Tracy S. Peterson, DVM, is a veterinary pathologist and PhD candidate in the aquatic animal health training program in the Department of Microbiology, all at Oregon State University, Corvallis.

Address correspondence and reprint requests to Dr. Jan Spitsbergen, Department of Microbiology, 220 Nash Hall, Oregon State University, Corvallis OR 97331 or email


During the past decade, the zebrafish has emerged as a leading model for mechanistic cancer research because of its sophisticated genetic and genomic resources, its tractability for tissue targeting of transgene expression, its efficiency for forward genetic approaches to cancer model development, and its cost effectiveness for enhancer and suppressor screens once a cancer model is established. However, in contrast with other laboratory animal species widely used as cancer models, much basic cancer biology information is lacking in zebrafish. As yet, data are not published regarding dietary influences on neoplasm incidences in zebrafish. Little information is available regarding spontaneous tumor incidences or histologic types in wild-type lines of zebrafish. So far, a comprehensive database documenting the full spectrum of neoplasia in various organ systems and tissues is not available for zebrafish as it is for other intensely studied laboratory animal species. This article confirms that, as in other species, diet and husbandry can profoundly influence tumor incidences and histologic spectra in zebrafish. We show that in many laboratory colonies wild-type lines of zebrafish exhibit elevated neoplasm incidences and neoplasm-associated lesions such as heptocyte megalocytosis. We present experimental evidence showing that certain diet and water management regimens can result in high incidences of neoplasia and neoplasm-associated lesions. We document the wide array of benign and malignant neoplasms affecting nearly every organ, tissue, and cell type in zebrafish, in some cases as a spontaneous aging change, and in other cases due to carcinogen treatment or genetic manipulation.

Key Words: Danio rerio; diet; hepatocyte megalocytosis; husbandry; naturally occurring carcinogen; neoplasia; nonprotocol-induced variation; zebrafish

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