Studies on the proliferation and fate of oval cells in the liver of rats treated with 2-acetylaminofluorene and partial hepatectomy.

The kinetics of oval cell proliferation in the liver and their fate were studied by combined autoradiography and immunohistochemical staining for epidermal prekeratin and epoxide hydrolase (EH). The oval cell proliferation was induced in rats by exposure to dietary 2-acetylaminofluorene (2-AAF) for 2 weeks with the midway performance of partial hepatectomy (PH). The labeling with 3H-thymidine [3H-TdR] was done in different groups of rats by two procedures: continuous exposure for 1 week with the aid of a minipump and brief exposure by the administration of a single dose. The livers of groups of animals were examined from 1 to 10 weeks after PH. Oval cells and duct epithelium showed positive staining for prekeratin and negative for EH, whereas hepatocytes showed the reverse pattern of staining. A critical finding was the observation that the exposure to the 2-AAF inhibited virtually completely the labeling of hepatocytes with [3H]-TdR in the caudate lobe and incompletely in the right lobe without interfering with the labeling of the oval cells in either lobe. This made it possible to study the fate of the oval cells vis-à-vis hepatocytes. This qualitative-quantitative study of oval cells and hepatocytes clearly indicates that oval cells under these experimental conditions do not become hepatocytes within 10 weeks. Over 80% of oval cells disappear within this period, and the remainder persist as such. These results indicate that under one set of experimental conditions related to hepatocarcino-genesis in the rat, no evidence for the conversion of oval cells to hepatocytes was obtained.