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Toxicologic Pathology
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Zonal Distribution of Cell Proliferation in the Liver of Untreated B6C3F1 and C57BL Mice

Silke Burkhardt

Institut für Veterinär-Pathologie, Justus-Liebig-Universität Giessen, Germany, BASF-AG, Ludwigshafen, Germany, silke.burkhardt{at}basf-ag.de

Rainer Bahnemann

BASF-AG, Ludwigshafen, Germany

Klaus Failing

Arbeitsgruppe Biomathematik und Datenverarbeitung, Institut für Veterinär-Physiologie, Justus-Liebig-Universität Giessen, Germany

Manfred Reinacher

Institut für Veterinär-Pathologie, Justus-Liebig-Universität Giessen, Germany

To determine the lobular distribution of hepatocellular proliferation, S-phase response was measured in untreated adult male B6C3F1 and C57BL mice at ages 11, 14, and 23 weeks. The percentage of cells in S-phase (labeling index, LI) was evaluated using immunohistochemical detection of 5-bromo-2'-deoxyuridine (BrdU). The BrdU was delivered either by a single ip injection 2 hr prior to sacrifice or via an osmotic minipump implanted subcutaneously for 3 or 7 days. Mitotic and apoptotic indices were determined on H&E stained sections. Animals of both strains and all ages revealed highest LI in the intermediate compartment of the liver acinus (zone 2) irrespective of the length of BrdU application. Cell proliferation in this zone was at all time points significantly higher than elsewhere in the liver. The mitotic index confirmed the data obtained by the S-phase response study. Apoptosis was rarely observed. With regard to rodent data in chemical carcinogenesis and the way they should be evaluated, this study proved that the acinar distribution of proliferating cells in liver of mice is different from that in rats, since, according to the literature, rats reveal highest cell proliferative activity in the periportal zone.

Key Words: Cell proliferation • apoptosis • labelling index • BrdU • mouse • liver.

Toxicologic Pathology, Vol. 32, No. 1, 100-105 (2004)
DOI: 10.1080/01926230490266000
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