Development of aquarium fish models for environmental carcinogenesis: Tumor induction in seven species
ABSTRACT 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.
- [Show abstract] [Hide abstract]
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-Carcinogen12/2010: pages 197-218;
Article: Zebrafish models of germ cell tumor.[Show abstract] [Hide abstract]
ABSTRACT: Germ cell tumors are neoplasms arising from pluripotent germ cells. In humans, these tumors occur in infants, children and young adults. The tumors display a wide range of histologic differentiation states which exhibit different clinical behaviors. Information about the molecular basis of germ cell tumors, and representative animal models of these neoplasms, are lacking. Germline development in zebrafish and humans is broadly conserved, making the fish a useful model to probe the connections between germ cell development and tumorigenesis. Here, we provide an overview of germline development and a brief review of germ cell tumor biology in humans and zebrafish. We also outline some methods for studying the zebrafish germline.Methods in cell biology 01/2011; 105:3-24. · 1.44 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: The small vertebrate, zebrafish, has generated a big wave in current biomedical research. In the early experiments of carcinogen treatment, it has been found that the induced tumors in the zebrafish share many similar features with those of humans. With the recent development in transgenic technology, we are able to control the expression of a specific oncogene in targeted organs for generation of different tissue tumor models in zebrafish. In particular, the fusion of an oncogene and a color reporter, such as the green fluorescent protein, allows us to conveniently monitor transgenic tumors for their initiation, progression, metastasis and transplantation in the transparent zebrafish embryos, as demonstrated in this article with our newly established liver cancer models. What does the future hold in this rapidly growing model organism? Other than understanding the molecular mechanisms of carcinogenesis, one obvious area will be the potential of these models for rapid and high-throughput screening for anticancer drugs.Future Oncology 01/2012; 8(1):21-8. · 3.20 Impact Factor