not precisely known, but clonal growth of hepatocytes in each cirrhotic nodule has been established. 10 However, as multiple steps in carcinogenesis are required, clonal growth ABSTRACT may be an early rather than a final event. Is there an ''un-
The regulation of the inositol 1,4,5-trisphosphate (IP 3 ) reknown'' toxin such as ''hepatocarcinin''? 11 Because the inciceptor in liver was analyzed using a novel superfusion dence of HCC also varies with the underlying cause and stage method. Hepatic microsomes were loaded with 45 Ca 2/ , and of cirrhosis, the etiology of cirrhosis in this North American superfused at high flow rates to provide precise control over series is of interest. Alcoholism and hepatitis B virus were IP 3 and Ca 2/ concentrations ([Ca 2/ ]) and to isolate 45 Ca 2/ significant factors related to HCC in this series. Hepatitis C release from reuptake. 45 Ca 2/ release was dependent on both virus data were not available for much of this study period, [Ca 2/ ] and IP 3 . The initial rate of 45 Ca 2/ release was a biphasic and thus its role is not confirmed in this study. This expert function of [Ca 2/ ], increasing as [Ca 2/ ] approached 3 mmol/ pathology group is in the process of writing the third edition L but decreasing at higher concentrations, suggesting that the of the AFIP fascicle on liver tumors, and many other features hepatic IP 3 receptor is regulated by [Ca 2/ ] at two sites, a high of this large series are likely to be developed and reported.
affinity potentiation site and a low affinity inhibitory site. The Related topics of histological interest not covered in this relationship between initial rates and IP 3 concentration was current series include incidence data on some unusual substeep (Hill coefficient of 3.4), suggesting that activation of the types of HCC, such as sarcomatoid HCC and the combined calcium channel requires binding of at least 3 IP 3 molecules. HCC/cholangiocarcinoma. IP 3 concentrations above 10 mmol/L produced rapid decay of release rates, suggesting receptor inactivation. Superfusion JOHN R. CRAIG, M.D., Ph.D. with 10 mmol/L IP 3 under conditions that minimize calcium Department of Pathology release ([Ca 2/ ]) 1 nM) inhibited 45 Ca 2/ release in response University of Southern California to subsequent stimulation (400 nmol/L Ca 2/ ). These data sug-St. Jude Medical Center gest sequential positive and negative regulation of the hepatic Fullerton, CA IP 3 receptor by cytosolic calcium and by IP 3 , which may underlie hepatocellular propagation of regenerative, oscillatory