Effects of temperature and partial hepatectomy on the induction of liver tumors in Oryzias latipes.

When the medakas, Oryzias latipes, were treated with diethylnitrosamine (DENA) for 6-8 weeks, large liver tumors grew in many of them at 11-13 weeks. In the fish with fully developed tumors, some aneuploid hepatic cells, detected by DNA-Feulgen cytofluorometry, were already found after 3-6 weeks of the DENA treatment. The allogeneic transplantation of liver grafts into eye chambers showed that the grafts obtained from DENA-treated or tumor-bearing fish could survive for longer periods than those from untreated fish. Effects of temperature on liver tumorigenesis were examined at 5-8 degrees C and at 22-25 degrees C. When the fish were treated with DENA at a high temperature, small tumor foci appeared during the treatment, and they grew to large tumors if the fish were kept at a high temperature afterward. Most of the fish had no tumors with the treatment given at a low temperature. Only a few tumors were found in the fish treated with DENA at a low temperature and then kept at a higher one. In the measurement of the labeling and mitotic indexes of liver cells, DNA synthesis and cell divisions occurred during the DENA treatment at a high temperature. A close relationship between cell proliferation and appearance of the histological changes in liver tissue was observed. Three to 4 days after a partial hepatectomy was performed on each medaka, mitotic figures of liver cells were frequently observed, and the maximum mitotic index of more than tenfold the control level was obtained at 4 days. The enhancing effect of the partial hepatectomy on the liver tumorigenesis by DENA treatment was examined.