Chemically-induced hepatocycte proliferation in the medaka (Oryzias latipes)

Several known mammalian carcinogens were examined for their ability to induce proliferation in hepatocytes of the medaka (Oryzias latipes). Compounds tested were N-nitrosodiethylamine (DEN), acrylonitrile (AN), 4-aminobiphenyl (4ABP) and methapyrilene (MP). Cell proliferation was assessed by proliferating cell nuclear antigen (PCNA) immunohistochemistry. Statistically significant increases in PCNA labeling indices (LIs) occurred following exposure to DEN, AN and 4ABP. Exposure to MP resulted in an apparent, but not statistically significant, LI increase. Proliferation, however, was not correlated with subsequent carcinogenesis except in the case of DEN. AN, 4ABP and MP were not carcinogenic to medaka in bioassays. Overall, cell proliferation appears to be a marker of chemically-induced cytotoxicity in medaka, but its relationship to carcinogenesis is presently not clear.