Hepatopathology of diethylnitrosamine in the medaka (Oryzias latipes) following short-term exposure

Abstract

The effect of short-term exposure (48 hr) of 14-day-old medaka (Oryzias latipes) to diethylnitrosamine (DEN) was tested on 4 groups of fish at 0, 100, 200, and 400 mg/L, with interim sacrifices of up to 6 months post exposure. Many of the lesions seen were similar to those seen in other fish DEN carcinogenicity studies using longer term, adult exposures, including a cytotoxic phase with cystic degeneration of the hepatic parenchyma, cellular vacuolation, globular acidophilic cytoplasmic inclusions, spongiosis hepatis, foci of cellular alteration, adenomas, and cholangiomas. There were also several proliferative lesions of uncertain origin which occurred throughout the study. There appeared to be a direct relationship between exposure level and the incidence and severity of the lesions seen, including aggressiveness and invasiveness of the neoplasms seen. However, there was a possible difference from other studies in the types of neoplasms seen with this protocol, which may be related to age at exposure, exposure level, duration of exposure, or a combination of these factors. Similarities in lesions seen in this study and in rodent and other fish studies is an indication of promise for the use of this model in carcinogenicity testing. Differences indicate the variety of ways the fish liver can respond to toxic injury, and lend flexibility to the model.