Carcinogenesis, Vol 19, 2069-2080, Copyright © 1998 by Oxford University Press
P Strobel, F Klimek, H Zerban, A Kopp-Schneider and P Bannasch
Tigroid cell foci (TCF) are a well-defined entity induced in rat liver by
chemical carcinogens, their significance for hepatocarcinogenesis being
controversial. Using cytomorphological, cytochemical and morphometric
approaches, we studied the evolution and fate of TCF sequentially from 7 to
110 weeks in groups of 50 male Sprague-Dawley rats, which remained
untreated or received N-nitrosomorpholine (NNM) orally at concentrations of
3 and 1 mg/kg body wt/day for 7 and up to 75 weeks, respectively. An
increased incidence of hepatocellular neoplasms developed in exposed
animals compared with controls, which was significant for adenomas at both
dose levels, and for carcinomas (HCC) after the longer exposure to the
lower dose level (P < 0.0001). TCF appeared frequently in addition to
other types of proliferative foci of altered hepatocytes (FAH) including
clear/acidophilic and mixed cell foci (MCF) in NNM-treated and rarely in
untreated rats. Striking similarities in the cellular phenotypes of TCF and
many hepatocellular neoplasms indicated the potential of TCF for
progression to both adenomas and carcinomas. TCF emerged from xenomorphic
cell foci (XCF), which consisted of hypertrophied hepatocytes typically
presenting an enlarged nucleus, abundant glycogen, smooth and rough
endoplasmic reticulum, altered activities of several enzymes of
carbohydrate metabolism and an increased cell proliferation (P < 0.001)
compared with the extrafocal parenchyma. TCF shared many features with XCF,
but their basophilia and proliferative activity was higher. The number of
FAH appearing at the two dose levels of NNM was similar but the average
size of TCF and MCF was frequently higher at late time points in the group
developing a significantly higher incidence of HCC, which suggests a
pronounced acceleration of neoplastic conversion in established
preneoplastic cell populations rather than the induction of additional FAH
by sustained effects of low doses of carcinogens.
ARTICLES
Xenomorphic hepatocellular precursors and neoplastic progression of tigroid cell foci induced in rats with low doses of N-nitrosomorpholine
Division of Cell Pathology, Deutsches Krebsforschungszentrum, Abteilung Cytopathologie (C0100), Heidelberg, Germany.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  F. Dombrowski, C. M. Jost, S. Manekeller, and M. Evert Cocarcinogenic Effects of Islet Hormones and N-Nitrosomorpholine in Hepatocarcinogenesis after Intrahepatic Transplantation of Pancreatic Islets in Streptozotocin-Diabetic Rats Cancer Res., August 1, 2005; 65(15): 7013 - 7022. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Bannasch Comments on R. Karbe and R. L. Kerlin (2002). Cystic Degeneration/Spongiosis Hepatis (Toxicol Pathol 30 (2), 216--227) PETER BANNASCH Toxicol Pathol, August 1, 2003; 31(5): 566 - 570. [Abstract] [PDF]
|
|
|
|
|
|
T. Harada, S. Yamaguchi, R. Ohtsuka, M. Takeda, H. Fujisawa, T. Yoshida, A. Enomoto, Y. Chiba, J. Fukumori, S. Kojima, et al. Mechanisms of Promotion and Progression of Preneoplastic Lesions in Hepatocarcinogenesis by DDT in F344 Rats Toxicol Pathol, January 1, 2003; 31(1): 87 - 98. [Abstract] [PDF]
|
|