Development of Aquarium Fish Models for Enviornmental Carcinogenesis: Tumor Induction in Seven Species

Journal of Applied Toxicology (Impact Factor: 2.98). 08/1985; 5(4):261 - 264. DOI: 10.1002/jat.2550050408


For small fish species to be utilized as models for carcinogenicity testing they should be capable of developing neoplasms, preferably in multiple tissues, when exposed to known carcinogens. Seven species of small fish were exposed to methylazoxymethanol acetate (MAM-Ac) and tumor development was monitored. Specimens 6–10 days old were exposed to nominal concentrations of MAM-Ac up to 100 mg l−1 for 2 h, then transferred to carcinogen-free water. Hepatic neoplasms developed in the Japanese medaka, guppy, sheepshead minnow, Gulf killifish, inland silverside, rivulus, and fathead minnow. Additionally, neoplasms occurred in other organs and tissues of the medaka (retina, various mesenchymal tissues, exocrine pancreas, kidney, and nervous tissue), guppy (mesenchymal tissue, exocrine pancreas, and kidney), and sheepshead minnow (choroid gland, mesenchymal tissues, and nervous tissue). All tumors were diagnosed in specimens within 1 year post-exposure. Early signs of liver tumors appeared in medaka and guppy at about 1 month post-exposure. These studies show that both medaka and guppy would be good models because they appear sensitive to carcinogens, develop tumors in multiple tissues and are easy to breed and maintain. Certain other small fish species also may prove to be good models because of habitat preferences, breeding strategies, or genetic attributes.

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    • "A great advantage of small aquarium fi sh for cancer bioassays has been their low background tumor incidences in comparison with mammals (Hawkins et al. 1985, 2003; Spitsbergen et al. 2000a, 2000b). Recently, we have found that water system design and diet exert profound effects on spontaneous tumor incidences in zebrafi sh. "
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    ABSTRACT: 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.
    ILAR journal / National Research Council, Institute of Laboratory Animal Resources 06/2012; 53(2):114-25. DOI:10.1093/ilar.53.2.114 · 2.39 Impact Factor
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    • "Actually, the use of zebrafish for carcinogenicity testing of chemicals and in toxicology long predates their use as a genetic model (Stanton 1965). The zebrafish has been also utilized in carcinogenesis studies to evaluate the risk from environmental hazards such as carcinogens in drinking water (Hawkins et al. 1985). Zebrafish inhabiting natural waters also serves as an important sentinel to indicate carcinogenic risks in the environment (Hawkins et al. 1995). "
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    ABSTRACT: The zebrafish (Danio rerio) has been increasingly recognized as a promising animal model for cancer research. Zebrafish tumors can be generated by treatment with chemical carcinogens or by genetic approaches. The liver has been a main target organ for tumorigenesis after carcinogen treatment while many other tissue-specific tumors have been generated by tissue-specific expression of proven oncogenes. We have used both the chemical and transgenic approaches to generate liver tumors. By comparative analyses of transcriptome profiles between human liver tumors and carcinogen-induced zebrafish liver tumors, we have demonstrated a remarkable similarity in the molecular hallmarks during liver tumorigenesis between humans and zebrafish, thus validating the zebrafish model for human cancer studies. Recently, we have also generated stable transgenic zebrafish lines overexpressing the c-Myc and kras V12 in the liver using two different inducible gene expression systems. In both cases, we found that tumors can be reproducibly induced in the liver, and histopathological examination confirmed the production of liver neoplasia including heptocellular carcinoma. Thus, we have successfully established transgenic zebrafish models for liver cancers and these models will be further characterized in order to understand the molecular and genetic mechanisms of liver carcinogenesis as well as for anti-cancer drug discovery. KeywordsZebrafish-Hepatocellular carcinoma-Transgenic-Kras-c-Myc-Carcinogen
    Molecular Genetics of Liver Neoplasia, 12/2010: pages 197-218;
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    • "Despite more than 300 million years separating the last common ancestor of fish and humans, the biology of cancer is very much the same in these two organisms. Cancer is commonly seen in fish in the wild, and straightforward assays involving water-borne carcinogen exposure have demonstrated that teleosts develop a wide variety of benign and malignant tumors in virtually all organs, with a histology closely resembling that of human tumors (Hawkins et al., 1985; Spitsbergen et al., 2000). A comparison of the human genome sequence and the soon to be completed zebrafish sequence demonstrates conservation of cell-cycle genes, tumor suppressors, and oncogenes. "
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    ABSTRACT: Although the zebrafish model provides an important platform for the study of developmental biology, recent work with the zebrafish model has extended its application to a wide variety of experimental studies relevant to human disease. Currently, the zebrafish model is used for the study of human genetic disease, caveolin-associated muscle disease, homeostasis, kidney development and disease, cancer, cardiovascular disorders, oxidative stress, caloric restriction, insulin-like pathways, angiogenesis, neurological diseases, liver disease, hemophilia, bacterial pathogenesis, apoptosis, osteoporosis, immunological studies, germ cell study, Bardet-Biedl syndrome gene (BBS11), Alzheimer's disease, virology studies and vaccine development. Here we describe the essential use of the zebrafish model that applies to several clinical diseases. With increased understanding of the cellular mechanisms responsible for disease, we can use knowledge gained from the zebrafish model for the development of therapeutics.
    Current Neurovascular Research 06/2007; 4(2):111-20. DOI:10.2174/156720207780637234 · 2.25 Impact Factor
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