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

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