TISSUE PROTEIN-TURNOVER DURING LIVER CARCINOGENESIS

Overall rates of tissue protein degradation in vivo during chemical he patocarcinogenesis were estimated by a double-isotope method as well a s from the accumulation of peptide intermediates in protein degradatio n induced by bestatin. Several parameters estimating rates of cell pro liferation and cell loss have been measured in parallel. The two proce dures adopted consistently indicated that protein turnover was signifi cantly slowed down through the whole observation period (12 months aft er the initiating administration of DENA) in both 'preneoplastic' nodu les and hepatomas as compared with control livers or perinodular tissu e. Such a difference may confer a selective growth advantage to 'prene oplastic' and tumoral cells. Since protein degradation rates did not a ppreciably differ between nodules and hepatomas, either such advantage originated from some early step in the carcinogenetic process or it m erely reflected the proliferative events in the two cell populations. Yet neither liver nodules nor hepatomas were characterized by very hig h rates of cell proliferation, however much increased with respect to control liver.