COMPARISON OF TWO DIFFERENT TREATMENTS TO INDUCE SUBCLINIC HEPATIC PRENEOPLASIA IN RATS

VERA MARINA C.; BIANCARDI,MARÍA E.; PISANI,GERARDO B.; BOTTAI, HEBBE; OCHOA, ELENA J.; MARTINEZ, ALEJANDRA; QUINTANA,ALEJANDRA

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Congreso; XV CONGRESS y XXXIII ANNUAL MEETING Sociedad de Biología de Rosario; 2013

Sociedad de Biología de Rosario

A model to induce subclinic hepatic preneoplasia (SHP) used dietilnisamyne (DEN, inductor) and 2-acetylaminofluorene (2-AAF, promoter) (DEN150 model). Both chemicals induce cholestasis and fibrosis. We compared DEN150 model whit other developed by us (DEN200), to induce SHP in an easier and less traumatic way for treated animals. Adult male Wistar rats (300-350 g) were divided in 3 groups (G, n=3 each). G1: control. G2, DEN150: 2 doses of DEN (150 mg/Kg body weight) were administrated i.p. 2 weeks apart and then 2-AAF (20 mg/Kg body weight) was given to rats by gavage 4 times per week, 3 weeks. G3, DEN200: a unique dose of DEN (200 mg/kg body weight) was administrated i.p. and 2 weeks later 2-AAF (equal dose and way of administration than in DEN150) was given 2 times per week, 3 weeks. GOT, GPT, Cholinesterase and prothrombin percentage (% P) were determinate. Liver samples were fixed in 10 % formaldehyde and process for paraffin embedded. With H&E we analyze cholestasis counting the number of bile ductules (BD) in 20 microscopic fields, expressed as Nº BD/microscopic field. With Direct Red 80/Picric Acid we studied fibrosis measuring total collagen amount (TC) by a computerized image method in 10 microscopic pictures of each animal (n=3) from of each G and expressed as area occupied by TC/picture area. With anti rGST-P: we determinate the presence of prenopastic foci (PF). PF were estimated as percentage of the total tissue. DEN200 had fewer BD and less fibrosis than DEN150 and developed fewer PF. DEN200 is effective to induce SHP in better conditions for rats.