William E. Hawkins; William W. Walker; Robin M. Overstreet
Availability, economy, latency of tumorigenic response, and ease of
maintenance and exposure are commonly cited advantages of small fish species in carcinogenesis
bioassays. Furthermore, carcinogen metabolism and mechanisms of carcinogenesis in small fish
species appear similar to those processes in large fish as well as in rodents. Practically,
small fish can be used to test waterborne carcinogens having a variety of expected mechanisms.
Direct-acting genotoxic carcinogens are tested in brief static exposures. Seven species exposed
to methylazoxymethanol acetate (MAM-Ac) under identical conditions demonstrated species
dependent neoplasms latencies, dose responses, and types of neoplasms induced. MAM-Ac exposures
further revealed two new tumor models, retinal medulloepitheliomas in Japanese medaka and
exocrine pancreatic neoplasms in the guppy. The retinal neoplasms involved elements of both
sensory retina and pigment epithelium and their analysis should lead to a better understanding
of several retinal neoplasms in other organisms. The pancreatic neoplasms involved mainly acinar
cell neoplasms. Most indirect acting genotoxic carcinogens require longer exposures than
direct-acting ones. Polynuclear aromatic hydrocarbons such as benzo(a)pyrene (BaP) and
7,12-dimethylbenzanthracene (DMBA) induce tumors in medaka and guppy following waterborne
exposures. BaP induced liver tumors in both species whereas DMBA induced several types of
extrahepatic tumors as well as hepatic ones. Preliminary studies also indicate that some
halogenated organic compounds cause hepatic neoplasms in exposed medaka and guppy. This study
was supported by Public Health Service contract N01CP26008/61070 from The National Cancer
Institute, the U.S. Army Medical Research and Development Command, and by the American Petroleum
Institute.