HEPATIC OVAL CELL ACTIVATION IN RESPONSE TO INJURY FOLLOWING CHEMICALLY-INDUCED PERIPORTAL OR PERICENTRAL DAMAGE IN RATS

Administration of 2-acetylaminofluorene (2-AAF) given before partial h epatectomy (PHx) results in suppression of hepatocyte proliferation an d stimulation of oval cell proliferation. Our objective in this study was to examine the oval cell response and associated alpha-fetoprotein (AFP) gene expression by combining 2-AAF with selective damage of cen trilobular regions (carbon tetrachloride [CCl4]) or periportal regions (allyl alcohol [AA]). Centrilobular damage results in a more enhanced oval cell response and AFP gene expression than periportal damage. Co nversely, more intense proliferation of intraportal bile duct epitheli a was seen with 2-AAF/AA than with 2-AAF/CCl4. The oval cell response and AFP gene expression was ranked as 2-AAF/CCl4 greater than or equal to 2-AAF/PHx > 2-AAF/AA. AFP mRNA expression was also examined in an acute AA and CCl4 injury. We found very little AFP gene expression com pared with the 2-AAF/hepatic injury models. To see a true oval cell re sponse, the hepatocytes must be inhibited from proliferating. In addit ion, the results presented with the 2-AA/AA model suggest that the per iportal matrix may be as important as the cells that populate the area .