The Sensitivity of Rainbow Trout and Other Fish to Carcinogens

Abstract

Systematic design of replacement chemicals with reduced toxicities will require knowledge of mechanisms of action of parent compounds, especially in species which occupy the environment of most likely exposure. For aquatic systems, the rainbow trout has proven a valuable model for studying mechanisms of carcinogenicity. By comparison, small aquarium species show great potential as in situ field monitors of aquatic contamination by toxic chemicals but are less developed for mechanism studies. Fish species, especially rainbow trout, have also proven useful alternatives to traditional rodent models for comparative studies on mechanisms of action of nonaquatic carcinogens. These kinds of comparative studies form an essential basis for extrapolation of animal studies to man. Carcinogenicity testing of individual compounds and their replacements can provide only limited information on the expected impact of such chemicals on natural populations, since these populations are unavoidably exposed to potent modulators of the carcinogenic response. Hence any program which aims at redesign of commercial chemicals with reduced toxicities must have as a prior aim the full understanding of the mechanisms of joint carcinogen-inhibitor-promotor interactions. Because of their high sensitivity, low cost per individual, and low background tumor incidences, fish models such as the rainbow trout may be the only vertebrate models in which it is economically practical to initiate such complex studies.

N-Methyl-N'-Nitro-N-Nitrosoguanidine-Induced Neoplasms in Medaka (Oryzias latipes)*1

“…In fish, the effects of MNNG vary with species. In rainbow trout exposed to MNNG by dietary or aqueous routes, or by embryo injection, gastrointestinal, liver, kidney, and swim bladder neoplasms predominated (1,31,33,34,37,38). This contrasts with medaka, in which aqueously exposed adults or juveniles exhibited primarily skin, gill, olfactory, and reproductive and connective tissue neoplasms (29,30).…”

“…MNNG is a direct-acting carcinogen that has been shown to experimentally induce gastric neoplasms in dogs, rats, and hamsters with oral administration (20,(45)(46)(47) and sarcomas in rats by subcutaneous injection (46). Gastrointestinal, kidney, liver, and swim bladder neoplasms have also been induced in rainbow trout exposed to MNNG as embryo or fry by various routes (1,26,34). Adult medaka exposed to MNNG by aqueous route exhibited a surface-related distribution of neoplasms, including skin, gill, and olfactory tumors (29,30).…”

Initiation, Promotion, and Inhibition of Carcinogenesis in Rainbow Trout

“…Hepatocellular carcinoma is also the most common neoplastic response in trout (9,(24)(25)(26)(27)(28), though other neoplasms, including nephroblastoma, gastric and swim bladder papillary adenoma, and fibrosarcoma can be induced, depending on carcinogen used, exposure route, and dose. For example, dietary exposure to Nmethyl-N'-nitro-N-nitrosoguanidine (MNNG) induces only gastric papillary adenomas in rainbow trout, whereas embryonic or fry water exposure to a solution of MNNG also induces hepatocellular carcinoma, nephroblastoma, and swim bladder papillary adenoma (8). The malignancy of some of these neoplasms has been demonstrated by transplantation into isogenic hosts (29, and Hendricks and Bailey, unpublished results).…”

“…The response of rainbow trout and other laboratory fish models to known mammalian carcinogens has been recently reviewed (4,5,8,9), and will only be summa-rized here. Carcinogen classes tested have included: mycotoxins; polycyclic aromatic hydrocarbons (PAHs); nitrosamines, nitrosamides, and other alkylating agents; heterocyclic amines; steroids and cyclic lipids; chlorinated hydrocarbon pesticides; and azo compounds.…”

Compendium of the FY1990 and FY1992 Research Reviews for the Research Methods Branch

“…For the careful analysis of primary neoplasms and their metastatic sites, the small size of the medaka is providing a cost-effective means for screening all important visceral organs. Given the potential importance of meoaka as a vertebrate model, the need exists for a nutritionally adequate and consistent experimental diet for this species (Bailey et al, 1984;Consensus Committee, 1984). Our laboratory has developed a purified casein-based diet (PC diet) for the medaka (DeKoven et al, 1992).…”