CCL4-INDUCED LIVER-CIRRHOSIS AND HEPATOCELLULAR-CARCINOMA IN RATS - RELATIONSHIP TO PLASMA ZINC, COPPER AND ESTRADIOL LEVELS

A number of biochemical events accompany the development of chronic li ver disease and its evolution into hepatic cancer. Low plasma zinc and high plasma copper levels have been observed in individuals with adva nced hepatocellular liver disease. Moreover, many investigators have d emonstrated an increase in serum estradiol levels in individuals with chronic liver disease and hepatocellular carcinoma (HCC). In the prese nt study, the relationship between these biochemical events and HCC wa s investigated in an animal model. Specifically, carbon tetrachloride (CCL4) was administered intragastrically to 20 female Sprague Dawley r ats for 30 weeks. All 20 animals developed cirrhosis. Six (30%) develo ped HCC. Signifi cantly higher serum estradiol, zinc and copper levels were observed in the rats developing HCC as compared with those with cirrhosis alone (P less than or equal to 0.05, 0.01 and 0.001, respect ively). A trend toward increased serum levels of progesterone, ALT and total bilirubin (0.1 greater than or equal to P less than or equal to 0.05) was found in the animals developing HCC. Na differences in seru m testosterone and alkaline phosphatase levels were noted between anim als with and without HCC. These studies demonstrate that in animals wi th experimental CCL4-induced cirrhosis and HCC serum levels of estradi ol, zinc and copper are increased, as is the case in man.