The State of the Art of the Zebrafish Model for Toxicology and Toxicologic Pathology Research—Advantages and Current Limitations

Spitsbergen, Jan M.; Kent, Michael L.

doi:10.1080/01926230390174959

Cited by 190 publications

(166 citation statements)

References 537 publications

(412 reference statements)

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“…The full response of zebrafish to dietary aflatoxins is not known, but Troxel and colleagues (1997) have shown that zebrafish can metabolize aflatoxin B1 postinjection, exhibiting some resistance to hepatocarcinogenicity. In addition, Spitsbergen and Kent (2003) found that all life stages of wild Florida zebrafish were remarkably resistant to aflatoxin B1, but little is known about inbred research strains held in long-term culture. Doubt about the quality of a diet should always result in its discard.…”

Section: Diet Developmentmentioning

confidence: 99%

Fundamental Approaches to the Study of Zebrafi sh Nutrition

Watts¹,

Powell²,

D’Abramo³

2012

ILAR Journal

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The value of the zebrafish model has been well established. However, culture variability within and among laboratories remains a concern, particularly as it relates to nutrition. Investigators using rodent models addressed this concern several decades ago and have developed strict nutritional regimes to which their models adhere. These investigators decreased the variability associated with nutrition in most studies by developing standardized reference and open formulation diets. Zebrafish investigators have not embraced this approach. In this article, we address the problems associated with the lack of nutritional information and standardization in the zebrafish research community. Based on the knowledge gained from studies of other animals, including traditional research models, other fish species, domesticated and companion animals, and humans, we have proposed an approach that seeks to standardize nutrition research in zebrafish. We have identified a number of factors for consideration in zebrafish nutrition studies and have suggested a number of proposed outcomes. The long term-goal of nutrition research will be to identify the daily nutritional requirements of the zebrafish and to develop appropriate standardized reference and open formulation diets.

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Section: Diet Developmentmentioning

confidence: 99%

Fundamental Approaches to the Study of Zebrafi sh Nutrition

Watts¹,

Powell²,

D’Abramo³

2012

ILAR Journal

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“…Despite the high level of sophistication of genetic and genomic tools available for the zebrafish model, basic pathology data for this species still lag far behind the data available for most mammalian laboratory and domestic animal species. While we understand the genetics controlling induction of specific cancer types in zebrafish, little basic information is published regarding spontaneous tumor incidences or histologic types in commonly used wt or mutant lines (Smolowitz et al 2002 ; Spitsbergen et al 2009; Spitsbergen and Kent 2003). Because of a strong primary focus on cancer genetics, many of the recent reports of neoplasia in transgenic or mutant lines of zebrafish do not provide data regarding the spontaneous tumor incidences or histologic spectrum of neoplasia in the genetic lines of fish used in the research and do not report the incidences or morphologic diagnoses of all tumor types in mutant or carcinogen-treated fish.…”

Section: Introductionmentioning

confidence: 99%

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

Spitsbergen

Buhler²,

Peterson³

2012

ILAR Journal

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During the past decade the zebrafish has emerged as a leading model for mechanistic cancer research due to 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 to 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 (wt) lines of zebrafish. So far a comprehensive database documenting the full spectrum of neoplasia in various organ systems and tissues in not available for zebrafish as it is for other intensely studied laboratory animal species. This manuscript 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 wt 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.

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“…The carcinogenicity of diverse compounds at various stages in Florida wild-type zebrafish has been well documented; when treated at the fry or embryo stage, they display a variety of neoplasms derived from epithelial, mesenchymal, neural and neural-crest tissues (Pliss et al , 1982; Khudoley, 1984; Spitsbergen and Kent, 2003; Mizgireuv et al , 2004). These data demonstrated the ease of using zebrafish to assess carcinogen responses in vivo and its capacity for developing a diverse range of cancers that pathologically resemble tumor types in humans (Goessling et al , 2007).…”

Section: Introductionmentioning

confidence: 99%

Transgenic Expression of Walleye Dermal Sarcoma Virus rv-cyclin Gene in Zebrafish and Its Suppressive Effect on Liver Tumor Development After Carcinogen Treatment

et al. 2010

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A retrovirus homologue gene of cellular cyclin D1, walleye dermal sarcoma virus rv-cyclin gene (orf A or rv-cyclin), was expressed in the livers of zebrafish under the control of liver fatty-acid binding protein (lfabp) promoter. To prevent possible fatality caused by over-expression of the oncogene, the GAL4/UAS system was used to maintain the transgenic lines. Thus, both GAL4-activator, Tg(lfabp:GAL4), and UAS-effector, Tg(UAS:rvcyclin), lines were generated and the rv-cyclin gene was activated in the liver after crossing these two lines. Since no obvious neoplasial phenotypes were observed in the double-transgenic line, cancer susceptibility of the transgenic fish expressing rv-cyclin was tested by carcinogen treatment. Unexpectedly, transgenic fish expressing rv-cyclin gene (rvcyclin+) seemed to be more resistant to the carcinogen than were siblings not expressing this gene (rvcyclin−). Lower incidences of multiple and malignant liver tumors were observed in rvcyclin+ than in rvcyclin− fish, and the liver tumors in the rvcyclin+ group appeared later and less severe. These results suggest that expression of rv-cyclin protects the fish liver from carcinogen damage and delays onset of malignancy. This observation—from a transgenic fish model—may be relevant to studies of liver-cancer inhibition and regression.

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The State of the Art of the Zebrafish Model for Toxicology and Toxicologic Pathology Research—Advantages and Current Limitations

Cited by 190 publications

References 537 publications

Fundamental Approaches to the Study of Zebrafi sh Nutrition

Fundamental Approaches to the Study of Zebrafi sh Nutrition

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

Transgenic Expression of Walleye Dermal Sarcoma Virus rv-cyclin Gene in Zebrafish and Its Suppressive Effect on Liver Tumor Development After Carcinogen Treatment

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