Digestive Diseases and Sciences. VoL 40, No. 4 (April 1995), pp. 730-733 Increased Ducts Turnover of Intrahepatic Bile Induced by Bromobenzene G. ZAJICEK, MD, R. SHAMIR, MD, J. NORDENBERG, PhD, Y. SIDI, MD, and N. ARBER, MD Intrahepatic bile duct epithelium consists of two kinetic compartments: a progenitor (P) and a functional (Q) compartment. Hitherto bromobenzene was known to poison only hepato- cytes in the third acinus zone. The present experiment aims to demonstrate that bromoben- zene 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 pro- genitors in both cell lineages, as well as in the stem cell itself. KEY WORDS: bromobenzene; bile ducts; streaming; liver. Healthy renewing cells die at sites remote from their birthplaces. Throughout their lives, they advance along the tissue radius. Proliferating cells known as progenitors occupy the proximal radius portion (the P compartment), and nonproliferating or functioning cells are located at its distal part (the Q compart- ment). In the liver, 1 hr after labeling with [3H]thy- midine or BrdU, 95% of the labeled cells are located within 200 /~m of the portal tract rim. This area is defined as the P compartment. The remaining part of Manuscript received July 11, 1994; revised manuscript received October 21, 1994; accepted November 20, 1994. From the H. H. Humphrey Center for Experimental Medicine and Cancer Research Hebrew University-Hadassah Medical School; Department of Medicine D Beilinson Medical Center; and Department of Gastroenterology, Tel Aviv Medical Center, Sack- ler Faculty of Medicine, Tel Aviv University, Israel, This work was partially supported by a grant from the Israeli Ministry of Health. Address for reprint requests: Dr. Nadir Arber, Columbia Cancer Center, 701 W 168th St. Room 1509, New York, New York 10032. 730 the acinus, where cells remain unlabeled, is defined as the functional or Q compartment (1, 2). We have shown (3) that intrahepatic bile duct epithelium renews its cells continuously in the same way that epidermis or gastrointestinal mucosa does. It also consists of two kinetic compartments, a progen- itor (P) and a functional (Q) compartment. P feeds Q with cells. Bromobenzene (BZ) poisons predominantly hepa- tocytes in the third acinus zone (4-8). Following its injection into rats, hepatocytes in the third zone swelled and became necrotic. The damage was most pronounced on the second day and disappeared within a week when dead hepatocytes were replaced by new cells and the acinus regained a normal ap- pearance. Previously we have shown that necrotic cells are replaced by hepatocyte progenitors that stream into the third zone, and this cell stream is accelerated by BZ (9). Digestive Diseases and Sciences, Vol. 40, No. 4 (April 1995) 0163.2116/95/0400.0730507.5010© 1995PlenumPublishing Corporation