Regression of cholangiocyte proliferation after cessation of ANIT feeding is coupled
with increased apoptosis.
LeSage, Gene, Shannon Glaser, Yoshiyuki Ueno, Domenico Alvaro, Leonardo Baiocchi,
Noriatsu Kanno, Jo Lynne Phinizy, Heather Francis, and Gianfranco Alpini.
1Departments of Internal Medicine and 2Medical Physiology, 3Division of Research
and Education, Scott & White Hospital and The Texas A&M University System
Health Science Center, College of Medicine and 4Central Texas Veterans Health Care
System, Temple, Texas 76504; 5Third Department of Internal Medicine, Tohoku
University School of Medicine, Aobaku, Sendai, Japan; and 6Division of
Gastroenterology, University of Rome, La Sapienza, Rome, Italy
APStracts 8:0091G, 2001.
Cholangiocyte proliferation and loss through apoptosis occur in cholestatic liver diseases.
Our aim was to determine the mechanisms of apoptosis in an animal model of ductal
hyperplasia. Rats were fed a-naphthylisothiocyanate (ANIT) for 2 wk and subsequently
fed normal chow for 1, 2, and 4 wk. Proliferation was assessed in sections by
morphometry and in small and large cholangiocytes by proliferating cellular nuclear
antigen immunoblots and measurement of cAMP levels. Apoptosis and reactive oxygen
species (ROS) levels were also assessed. ANIT feeding increased small and large
cholangiocyte proliferation and apoptosis. Cessation of ANIT feeding was associated
with decreased proliferation and a further increase in apoptosis in small and large
cholangiocytes. Cholangiocytes from ANIT-fed rats or exposed to ANIT in vitro showed
increased apoptosis and ROS generation. ANIT-induced duct injury results in enhanced
proliferation and apoptosis in small and large cholangiocytes. The mechanism of ANIT-
induced apoptosis may be due to ROS generation induced directly by ANIT. Our model
has implications for understanding the pathophysiology of cholangiopathies
(characterized by the coexistence of cholangiocyte apoptosis and proliferation).
Received 10 January 2001; accepted in final form 8 March 2001
APS Manuscript Number G012-1.
Article publication pending Am J Physiol Gastrointest Liver Physiol
ISSN 1080-4757 Copyright 2001 The American Physiological Society.
Published in APStracts on 14 May 2001