A UNIQUE RAT MODEL OF BILE DUCTULAR HYPERPLASIA IN WHICH LIVER IS ALMOST TOTALLY REPLACED WITH WELL-DIFFERENTIATED BILE DUCTULES

A novel rat model was developed in which furan combined in a unique sy nergistic manner with bile duct ligation to induce replacement of most of liver with well-differentiated hyperplastic bile ductules. Multipl e tissue sections of liver from Fischer 344 male rats first subjected to a bile duct ligation and 1 week later given furan by gavage at 45 m g/kg body weight, once a day, five times weekly for 5 to 6 weeks, exhi bited a mean percent of bile ductule tissue per total liver section ar ea of 72.6 +/- 16.3% compared to control values of 20.0 +/- 4.2% for b ile duct-ligated rats that received corn oil by gavage instead of fura n and 11.9 +/- 3.1% for rats that were given a sham operation followed by furan. This dramatic difference was also reflected by the very hig h mean gamma-glutamyl transpeptidase specific activity of liver homoge nates from the bile duct-ligated/furan-treated rats, which was similar to 8 x 10(3) nmoles p-nitroaniline/ mg protein/hour versus values of similar to 2 x 10(3) for bile duct-ligated/corn oil control, similar t o 1 x 10(3) for sham-operated/furan-treated control, and 44.9 for untr eated rat. The data presented support a potentially powerful experimen tal model for investigating bile ductular cell functions, differentiat ion, and proliferation.