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Factors influencing methylazoxymethanol acetate initiation of liver tumors in Oryzias latipes: carcinogen dosage and time of exposure.

Hepatic tumors were produced in the medaka (Oryzias latipes) kept at 25 degrees C in aquaria after exposure to methyl azoxymethanol (MAM) acetate. The tumors, including trabecular carcinomas and cholangiomas, were observable after 2-3 months. A similar incidence, i.e., nearly 100%, was found after a long-time exposure to a low level (0.1 ppm for 120 days) and after a short exposure to a high level (10 ppm for 1 hr) of MAM acetate. The relationship between the level of MAM acetate (0-2.0 ppm) and tumor incidence was studied after exposure for 1 day. The incidence increased as the level of drug increased, although an apparent threshold was seen at low levels. The incorporation of [3H]thymidine into the liver greatly increased over the period of 6-20 days after treatment with 0.5 ppm for 3 days. However, only a slight increase in incorporation was found when fish were treated continuously with a low level (0.1 ppm) from days 30 through 90. No reduction of tumor incidence was found when the carcinogen was given in 2 divided doses separated by various intervals, compared with a single exposure.