In vivo apoptotic effect of Interferon alfa-2b (IFN) on rat preneoplastic liver

ALVAREZ M.L; CERLANI J.P; MONTI J; CARNOVALE C; RONCO T; PELLEGRINO J; PISANI G; LUGANO C; CARRILLO M.C

Madrid, España

Congreso; Biennal Meeting of the International Association for the Study of the Liver – 37 th Annual Meeting of the European Association for the Study of the Liver; 2002

International Association for the Study of the Liver -European Association for the Study of the Liver

In order to know whether IFN prevents in vivo oncogenesis in the very-early-stage cancer cells, we evaluated the action of IFN on hepatic preneoplastic foci in rats. Adult male Wistar rats were divided into six groups: subjected to an initiation-promotion model of cancer development (G1) (initiated with dietylnitrosamine and promoted with 2-acetylaminofluorene), treated with IFN during: a) initiation-promotion (G2), b) initiation (G3), promotion (G4); subjected only to an initiation stage (G5) and treated with IFN during this period (G6). The number and area of rGST P-positive foci were significantly reduced in G2, 3 and 6; but not in G4. Animals that received IFN during the initiation stage showed higher apoptotic index in altered hepatic foci (G1= 0.26+/-0.03; G2= 0.40+/-0.02*; G3= 0.42+/-0.02*; G4= 0.40+/-0.04; G5= 0.15+/-0.02; G6= 0.23+/-0.01#). Bax protein in liver lysates was increased in IFN-treated rats (G1= 100%; G2= 252+/-6%*; G3= 253+/-2%*; G4= 157+/-6%*; G5= 100%; G6= 335+/-14%#). Similarly, levels of the antiapoptotic proteins Bcl-2 and Bcl-xL in mitochondrial fraction were decreased. Finally, increased levels of Bax protein were localized in the mitochondria of rats that received IFN, at least during the initiation (G2, 3 and 6), whereas mitochondrial Bax expression was not increased in G4: G1= 100%; G2= 156+/-7%*; G3= 130+/-2%*; G4= 84+/-11%; G5= 100%; G6= 219+/-40%# (*p<0.05 vs. G1; # p<0.05 vs. G5). In conclusion, preneoplastic hepatocytes in the IFN-treated rats undergo programmed cell death as a primary result of a significant increase in the amount of Bax protein and its translocation to the mitochondria.