Experimental hepatic tumorigenicity by environmental hydrocarbon dibenzo[a,l]pyrene

There is an evident need of low-cost vertebrates to be used in experimental carcinogenesis. Medaka (Oryzias latipes) provide a useful vertebrate model system for investigating tissue tropism of carcinogens and the action mechanisms of environmental contaminants posing a potential risk to human health. Juvenile medaka 2 months of age fed diets containing 100 ppm (dry weight basis) dibenzo[a,l]pyrene (DBP) for 28 days responded with hepatic neoplasia predominately of hepatocellular origin. When sampled 9 months following the termination of carcinogen exposure, medaka showed 26% incidence of neoplasia and 25% hepatic neoplasia, compared with 8% total neoplasia and 0% hepatic neoplasia in control fish. The predominant spontaneous neoplasms in this group of medaka were ovarian germ cell tumors. Hepatic neoplasia occurred at a higher incidence in female DBP-treated medaka than in males (11/29 vs 5/36). Nonneoplastic lesions observed in the livers of DBP-exposed fish included spongiosis hepatis, globular hyaline eosinophilic cytoplasmic inclusions in hepatocytes, foci of hepatocellular degeneration, extensive cytomegaly, and karyomegaly of hepatocytes. No activating exon I mutations in the one ras protooncogene examined were detected among six liver neoplasms. These results indicate that medaka are sensitive to the tumorigenic effects of the environmental carcinogen DBP, administered by dietary exposure.