Carcinogenicity tests with small fish species

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.