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.
- SourceAvailable from: tpx.sagepub.com[Show abstract] [Hide abstract]
ABSTRACT: Tracie Eileen Bunton received a DVM degree from Michigan State University in 1977. After practicing small animal medicine for a year, she completed a combined Comparative Pathology residency/Ph.D. program in 1982 at the University of California at Davis. Her residency training included 3 yr at the California Regional Primate Research Center and, for her thesis, she studied the effects of glucocorticosteroids on lung development in the fetal rhesus macaque.Toxicologic Pathology 09/1996; 24(5):603-618. · 1.92 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: The principle of refinement of animal usage in toxicology dictates that the appropriateness of a particular animal species for a particular protocol or experiment be thoroughly explored. Species are selected all too often on the basis of convenience or tradition. Rats are traditionally used for acute lethality testing and carcinogenicity testing. Dogs are traditionally used as a “nonrodent” species for general toxicity assessments. This review seeks to make the case that, for both scientific and economic reasons, other species can be appropriately substituted for rats or dogs for general toxicity assessment studies. These alternative species need not be totally exotic, but can, in fact, be species used in other areas of toxicology. Earthworms and fish are nonvertebrate animals used in environmental assessment studies. Earthworms could be used for lethality assessment in place of rodents, particularly for “QC batch” release or toxicity rating purposes. Fish could be used to further define hepatic carcinogenicity. Guinea pigs are frequently used for dermatologic studies, but rarely for other purposes. While a rodent, the guinea pig possesses many physiologic and metabolic characteristics that may make it more appropriate than rats for the chronic testing of certain classes of chemicals (NSAIDs, peroxisomal proliferators). Ferrets have been well studied in teratologic assessments, but have not gained wide acceptance as a “nonrodent” model. This review discusses in detail the available technology and published data that justifies the expanded and appropriate use of these “alternative” species. Special emphasis is given to xenobiotic metabolism, which is a major determinant in speciesrelated differences in toxicity.International Journal of Toxicology 01/1990; 9(3):319-342. · 1.23 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: Development of carcinogenesis bioassays that utilize small fish species is important principally for investigating the causes of neoplasms in wild fishes and for providing alternative or supplementary models to rodent carcinogenicity tests. Availability, economy, latency of tumorigenic response, and ease of maintenance and exposure are commonly cited advantages of small fish species in carcinogenesis bioassays. Carcinogen metabolism and mechanisms of carcinogenesis in several small fish species appear similar to those processes in the more thoroughly studied large fish species as well as in rodents. Recent studies suggest that small fish species are appropriate test models for waterborne carcinogens having a variety of mechanisms. Several small fish species readily develop hepatic and non-hepatic neoplasms following brief static exposures to direct-acting genotoxic compounds such as methylazoxymethanol acetate (MAM-Ac) and N-methyl-N′-nitro-N-nitrosoguanidine (MNNG). Tumorigenic responses appear to be related to species and to various exposure factors. Indirect-acting genotoxic carcinogens such as nitrosamines and polynuclear aromatic hydrocarbons have not been thoroughly tested in small fish species but appear to require longer exposures than direct-acting ones to induce hepatic neoplasms. An especially important potential use of small fish carcinogenesis bioassays is in testing carcinogens that might have epigenetic mechanisms, especially complex mixtures that might affect man or the environment but are difficult to test in rodent models. Preliminary studies indicate that prolonged exposures of up to 6 months to a mixture of halogenated organic compounds result in hepatic neoplasms in two small fish species. To improve their usefulness and exploit small fish carcinogenesis models better, gaps in several areas need to be filled. These include (1) a better understanding of biological and nutritional requirements of test species as related to carcinogenesis, (2) a broader database on neoplastic responses of various species to various chemicals, and (3) development of special exposure methods and standardization of test protocols.Aquatic Toxicology 01/1988; 11:113-128. · 3.51 Impact Factor