Possible model of liver carcinogenesis using inhibitors of NAD+ ADP ribosyl transferase in rats.

The response of cellular NAD+ metabolism to DEN and/or ABA and the carcinogenesis of the liver initiated by DEN and ABA were studied in rats. The liver NAD+ level was depleted by an ip injection of 20 mg or 200 mg/kg body weight of DEN. ABA, administered ip at a dose of 600 mg/kg simultaneously with or 4 hours after DEN, prevented the depletion of NAD+ by DEN. These biochemical findings correlated with the changes of conspicuous intranuclear immunofluorescence of poly(ADP-ribose), which were studied by immunohistochemistry. When initiated by 20 mg/kg body weight DEN and 600 mg/kg ABA and then processed to selection pressure, the liver was found to be capable of developing hepatocellular carcinomas with or without PB promotion. These results suggest that the inhibition of poly(ADP-ribosylation) might lead to irreversible initiation of liver carcinogenesis by DEN in rats.