Inhibition of Cell Proliferation in the Livers of Hepatectomized Rats by a Rabbit Hepatic Chalone

Abstract

A purified chalone isolated from rabbit liver was tested in vitro on regenerating rat liver slices incubated with tritiated thymidine to determine more precisely the phase of the normal cell cycle that was blocked by that substance. Biochemical and radioautographic studies showed that the inhibition of tritiated thymidine incorporation during chromosomal DNA replication resulted chiefly from a block in the G(1)-S transition in the normal cell cycle. Under these conditions the chalone had little inhibitory effect on hepatocytes that were in the S phase of the cell cycle. The inhibitory effects of the liver chalone appeared to be specific for hepatocytes and no significant inhibition of cell division was observed when that compound was tested against intestinal villi or tongue epithelial cells of the rat. When, on the other hand, the purified chalone was injected into rats following partial hepatectomy, not only was an inhibition observed during the G(1)-S transition but an increase in the ratio of metaphases to anaphases was found, suggesting that a block also occurs at metaphase as a result of the action of the purified liver chalone used in this study. The injection of a crude supernatant fluid obtained from rabbit liver homogenates into partially hepatectomized rats resulted not only in a more pronounced block at the G(1)-S transition than was observed when the purified chalone was used, but the supernatant liquid also affected significantly DNA synthesis during the S phase of the cell cycle. These inhibitory effects were observed not only in hepatocytes but in intestinal epithelium and tongue epithelial cells of the rat as well. The rabbit liver supernatant fluid thus appears to contain, in addition to the liver chalone, one or more nonspecific inhibitors of DNA synthesis.