Preliminary studies on the usefulness of medaka, Oryzias latipes, embryos in carcinogenicity testing

Medaka (Oryzias latipes) embryos were exposed continuously for 10 days to diethylnitrosamine (DENA) at concentrations of 25, 50, or 100 ppm. Following exposure and after hatching, the embryos were placed in clean, carcinogen-free water. Fish were sampled for pathological examination after 1 month, 3, and 6 months. Grossly visible liver tumors were evident after 3 months in 10 and 30% of the fish treated with 50 and 100 ppm DENA, respectively. Following 6 months exposure, 4% of the fish treated with 25 ppm, 15% of those given 50 ppm, and 43% of those treated with 100 ppm DENA contained liver tumors. Focal areas consisting of 10 to 40 highly basophilic cells in the liver were noted at all the exposure concentrations. The incidence of the focal areas increased proportionately with the concentration of DENA and the age of the fish. Liver tumors were examined by light and electron microscopy. Most of the hepatic tumors were moderate to well-differentiated trabecular hepatomas, although 2 cholangiomas and 2 poorly differentiated hepatomas were noted. No liver lesions or tumors were observed in controls.