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 microg 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 microg 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 microg 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.
Hara
A
A
Department of Pathology, Gifu University School of Medicine, Japan.
Yoshimi
N
N
Yamada
Y
Y
Matsunaga
K
K
Kawabata
K
K
Sugie
S
S
Mori
H
H
D000236:Adenoma / Q000276:immunology / Q000473:pathology*; D000477:Alkylating Agents / Q000494:pharmacology; D000818:Animals; D000911:Antibodies, Monoclonal; D017209:Apoptosis; D002471:Cell Transformation, Neoplastic / Q000276:immunology; D006224:Cricetinae; D004052:Diethylnitrosamine / Q000494:pharmacology; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced / Q000276:immunology / Q000473:pathology*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D019014:fas Receptor / Q000502:physiology*
D000477:Alkylating Agents; D000911:Antibodies, Monoclonal; D019014:fas Receptor; D004052:Diethylnitrosamine