Increased turnover of intrahepatic bile ducts induced by bromobenzene.

Abstract

Intrahepatic bile duct epithelium consists of two kinetic compartments: a progenitor (P) and a functional (Q) compartment. Hitherto bromobenzene was known to poison only hepatocytes in the third acinus zone. The present experiment aims to demonstrate that bromobenzene affects also bile duct turnover. Thirty male adult rats received one intraperitoneal injection of bromobenzene and were sacrificed in groups of five at the following times: 1, 2, 3, 4, 7, and 14 days. They received [3H]thymidine 1 hr before sacrificing. Autoradiography was done. Bile ducts were evaluated in all portal tracts of the section. The number of epithelial cells in each duct cross section was counted and defined as bile duct class, which is roughly proportional to bile duct size. In each cross section the number of labeled cells was counted. Initially the labeling index was 0.76 +/- 0.3%. By day 3, it reached a peak of 4.1 +/- 1.1%, and then declined to its initial level. Following bromobenzene poisoning, hepatocyte and bile duct epithelia turn over in the same fashion. In both, labeling index and progenitor compartment size initially rise and return by the end of the first week to their initial level. We propose that bile duct epithelia and hepatocytes originate in one determined uncommitted stem cell that resides in the Herring duct. Bromobenzene-induced necrosis triggers proliferation of progenitors in both cell lineages, as well as in the stem cell itself.