CHARACTERIZATION OF CERTAIN HEPATOCYTE-PROLIFERATING AND OR PROTECTIVE FACTORS INDUCED BY THE SENSITIZATION OF FREEZING-THAWING HEPATIC TISSUE/

Although tumor cryosurgery would be expected to produce beneficial imm unological effects from the enhancement of anti-tumor activity, under certain conditions the tumor may become enlarged and metastases promot ed due to increased immunosuppressive activity and a high zone toleran ce. In the present study, we examined whether hepatocyte-proliferating factors were produced by the inoculation of freezing-thawing hepatic tissue (FTHT). Serum obtained from rats inoculated with FTHT increased DNA synthesis, according to measurement by [H-3]thymidine incorporati on in primary cultured rat hepatocytes. This increase was dependent on the serum concentration, with serum obtained on day 14 after the inoc ulation being the most potent for hepatocyte proliferation. The sensit ized serum promoted DNA synthesis nearly as much as serum obtained fro m a 70% hepatectomized rat, but slightly less than 10 ng/ml hepatocyte growth factor. The sensitized serum also protected hepatocytes from c arbon tetrachloride (CCl4)-induced hepatotoxicity. Optical density mea sured by the 3-(4,5-dimethyl-thiazole-2-yl)-2,5-diphenyl tetrozolium b romide (MTT) cytoxicity assay was increased, and the release of aspart ate aminotransferase, alanine aminotransferase, and lactate dehydrogen ase in medium was decreased by treating hepatocytes damaged by CCl4 wi th the sensitized serum. These results suggest that certain hepatocyte -proliferating and protective factors are induced in serum by the inoc ulation of freezing-thawing hepatic tissue, and that the sensitized se rum may be useful in the treatment of liver failure.