Effects of Fas-mediated liver cell apoptosis on diethylnitrosamine-inducedhepatocarcinogenesis in mice

The present study was designed to investigate the effect of Fas-mediated li ver cell apoptosis, induced by a hamster monoclonal antibody against mouse Fas antigen, on diethylnitrosamine (DEN)-induced hepatocarcinogenesis in mi ce. DEN (10 mu g g(-1), intraperitoneally (i.p.)) was given to 15-day-old m ale C3H/HeJ mice. Three weeks after DEN treatment, Fas-mediated liver cell apoptosis induced by anti-fas antibody resulted in a biphasic effect on ind uction of liver cell tumours, depending on dosage and time of antibody admi nistration. Single or multiple treatment with high dose anti-fas antibody ( 5 mu g animal(-1)), induced gross liver cell damage and decreased the incid ence of liver cell tumours in DEN-treated mice. In contrast, five treatment s with low dose anti-Pas antibody (2 mu g animal(-1)), induced dispersed lo calized liver cell damage and promoted the number of large-sized liver cell adenomas and hepatocellular carcinomas. These findings suggest that high d ose anti-Pas antibody has a marked effect on the clearance of DEN-initiated liver cells, whereas repeated administration of low dose anti-Pas antibody promotes hepatocarcinogenesis. It is concluded that Pas-mediated liver cel l apoptosis has a biphasic effect on hepatocarcinogenesis. (C) 2000 Cancer Research Campaign.