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

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 mal...

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Detalles Bibliográficos
Autores principales: Hara, A, Yoshimi, N, Yamada, Y, Matsunaga, K, Kawabata, K, Sugie, S, Mori, H
Formato: Texto
Lenguaje:English
Publicado: Nature Publishing Group 2000
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2363286/
https://www.ncbi.nlm.nih.gov/pubmed/10646906
http://dx.doi.org/10.1054/bjoc.1999.0944
Descripción
Sumario: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