PROMOTING EFFECT OF CITRULLINE IN HEPATOCARCINOGENESIS - POSSIBLE MECHANISM IN HYPERCITRULLINEMIA

Hypercitrullinemia (adult type), believed to be one of the hereditary urea cycle disorders, is known to be complicated by hepatocellular carcinoma at a high incidence (approximately 14%). Weinvestigated the relationship between this hypercitrullinemia and he‐patocarcinogenesis. After the addition of citrulline, incorporation of tritiated thymidine into primary cultured hepatocytes of adult rat increased in a dose‐dependent fashion in the range of 0.1 to 5 mmol/L. The citrulline‐added group also showed significant in‐crease in ornithine and polyamine contents in hepatpcytes. The incidence of epithelial cell foci in the in vivo‐in vitro tumor promotion analyzing system significantly rose in the group maintained with mmol/L citrulline and in the group maintained with 1.5 mmol/L phenobarbital. These findings suggest the possiblility that citrulline has a promotion effect on hepatocyte proliferation and that at high concentra‐tions it plays the role of a hepatocarcinogenesis pro‐moter.(HEPATOLOGY 1990; 11:819‐823.) Copyright © 1990 American Association for the Study of Liver Diseases