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. 2000 Jan 18;82(2):467–471. doi: 10.1054/bjoc.1999.0944

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

A Hara 1, N Yoshimi 1, Y Yamada 1, K Matsunaga 1, K Kawabata 1, S Sugie 1, H Mori 1
PMCID: PMC2363286  PMID: 10646906

Abstract

The present study was designed to investigate the effect of Fas-mediated liver cell apoptosis, induced by a hamster monoclonal antibody against mouse Fas antigen, on diethylnitrosamine (DEN)-induced hepatocarcinogenesis in mice. DEN (10 μg g–1, intraperitoneally (i.p.)) was given to 15-day-old male C3H/HeJ mice. Three weeks after DEN treatment, Fas-mediated liver cell apoptosis induced by anti-Fas antibody resulted in a biphasic effect on induction of liver cell tumours, depending on dosage and time of antibody administration. Single or multiple treatment with high dose anti-Fas antibody (5 μg animal−1), induced gross liver cell damage and decreased the incidence of liver cell tumours in DEN-treated mice. In contrast, five treatments with low dose anti-Fas antibody (2 μg animal−1), induced dispersed localized liver cell damage and promoted the number of large-sized liver cell adenomas and hepatocellular carcinomas. These findings suggest that high dose anti-Fas antibody has a marked effect on the clearance of DEN-initiated liver cells, whereas repeated administration of low dose anti-Fas antibody promotes hepatocarcinogenesis. It is concluded that Fas-mediated liver cell apoptosis has a biphasic effect on hepatocarcinogenesis. © 2000 Cancer Research Campaign

Keywords: Fas, apoptosis, diethylnitrosamine, mouse, hepatocarcinogenesis

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Selected References

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