Development of Carcinogenesis Bioassay Models: Response of Small Fish Species to Various Classes of Carcinogens.

摘要

We established that vinylidene chloride was carcinogenic to both the medaka and guppy, causing hepatic neoplasms in both species. Exposure to acetylaminofluorene resulted in the induction of hepatic neoplasms in both species but in higher incidences in the guppy than in the medaka. In studies of the metabolism of AAF by liver microsomes, the enhanced carcinogenicity of the AAF in the guppy was related to the ability of the guppy to produce more of the N-hydroxylated metabolite, the carcinogenic metabolite, than the medaka which produced more of the ring-hydroxylated metabolites which result in detoxification. Studies on the hepatic metabolism of ethylene dibromide in the medaka indicated that the carcinogenic mechanism of this compound is similar in this species to that in rodents and may depend and a phase II (detoxification) pathway to exert its carcinogenicity. The compounds were negative in our tests. We would prefer, however, to consider that these compounds showed no evidence of carcinogenicity in the fish models under the conditions of the tests rather than considering them non-carcinogenic in the test species.