Tissue protein turnover during liver carcinogenesis

Overall rates of tissue protein degradation in vivo during chemicalhepatocarcinogenesis were estimated by a double-isotope methodas well as from the accumulation of peptide intermediates inprotein degradation induced by bestatin. Several parametersestimating rates of cell proliferation and cell loss have beenmeasured in parallel. The two procedures adopted consistentlyindicated that protein turnover was significantly slowed downthrough the whole observation period (12 months after the initiatingadministration of DENA) in both ‘preneoplastic’nodules and hepatomas as compared with control livers or perinodulartissue. Such a difference may confer a selective growth advantageto ‘preneoplastic’ and tumoral cells. Since proteindegradation rates did not appreciably differ between nodulesand hepatomas, either such advantage originated from some earlystep in the carcinogenetic process or it merely reflected theproliferative events in the two cell populations. Yet neitherliver nodules nor hepatomas were characterized by very highrates of cell proliferation, however much increased with respectto control liver.