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Evaluation of zebrafish (Brachydanio rerio) as a model for carcinogenesis

Zebrafish (Brachydanio rerio) are small, freshwater teleost fishes in the family
Cyprinidae, the true minnows. They are native to the tropical latitudes of India, but
have become widespread through their use as aquarium fish and as models for several
branches of biological research. Their ease of rearing, short generation time, year-around
egg laying potential, brief developmental period, and embryo transparency
have made them especially desirable as models for developmental biology, genetics,
and neurobiology. Because of their popularity, they were also the first small
aquarium fish to be used as test organisms for carcinogenesis in the early 1960's.
For reasons that have never been stated, their use as a model for carcinogenesis
research did not continue. Due to the number of positive characteristics that this
species has, the goal of this research effort was to systematically evaluate the potential
of zebrafish for use as an environmental monitor, to evaluate the toxicology and carcinogenesis of surface and/or ground waters. The overall project was
multidisciplinary in nature, but the focus of this thesis research was on the whole
animal, dose-response to a number of well-known carcinogens, administered by
multiple exposure routes, and the pathological description of the resulting lesions.
Exposure to N-nitrosodiethylamine (DEN) and N-nitrosodimethylamine (DMN) in the
diet was ineffective, but static water bath exposure of fry and embryos to these
nitrosamines resulted in neoplasms, primarily in the liver. Embryo exposure to DEN
resulted in a low response of neoplasms in several other organs as well. Dietary
exposure of zebrafish to aflatoxin B₁ resulted in few hepatic neoplasms, revealing a
marked resistance to this carcinogen. Dietary exposure to methylazoxymethanol
acetate (MAM-Ac) produced mostly liver tumors, as did both fry and embryo water
bath exposures. Each water bath exposure also produced neoplasms at other tissue
and organ sites, but the embryo stage produced the greatest variety. These results
demonstrate a relative resistance to neoplastic development compared to the well-known
rainbow trout model. But in one comparative trial, zebrafish were similar to
Japanese medaka in their response to dietary MAM-Ac. The major limitation of this
species, that will prevent its use as a model for environmental monitoring, however,
is its narrow range of temperature tolerance. Temperatures below 15°C produce
marked sluggishness, and below 10-12°C cause anesthesia and death. Therefore, this
research indicates that this species is not as versatile as some other small fish species
for laboratory and especially field monitoring of environmental carcinogenic hazards. / Graduation date: 1997

Identiferoai:union.ndltd.org:ORGSU/oai:ir.library.oregonstate.edu:1957/28169
Date09 July 1996
CreatorsTsai, Hsi-Wen
ContributorsHendricks, Jerry D.
Source SetsOregon State University
Languageen_US
Detected LanguageEnglish
TypeThesis/Dissertation

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