Open AccessDisturbance of the Cell Cycle with Colchicine Enhances the Growth Advantage of Diethylnitrosamine‐initiated Hepatocytes in Rats
Author(s) -
Tsutsumi Masahiro,
Ohashi Kazuo,
Tsujiuchi Toshifumi,
Kobayashi Eisaku,
Kobitsu Kunihiko,
Kitada Hiromichi,
Majima Toshimitu,
Okajima Eijiro,
Endoh Takehiro,
Hasegawa Kiyohiko,
Mori Toshio,
Konishi Yoichi
Publication year - 1996
Publication title -
japanese journal of cancer research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 0910-5050
DOI - 10.1111/j.1349-7006.1996.tb00192.x
Subject(s) - colchicine , cell growth , hepatocyte , endocrinology , chemistry , cell cycle , medicine , disturbance (geology) , cell , biology , biochemistry , in vitro , paleontology
The effect of cell cycle disturbance due to colchicine on the induction of enzyme‐altered foci during liver regeneration in rats was studied. For initiation, diethylnitrosamine (DEN) at a dose of 10 mg/ kg was injected intraperitoneally and partial hepatectomy (PH) was performed 4 h thereafter. Colchicine at doses of 0, 0.1, 0.25 and 0.5 mg/kg was injected intraperitoneally 1 and 3 days after the initiation, followed by application of selection pressure consisting of 2‐acetylaminofluorene (AAF) and carbon tetrachloride (CCl 4 ) administration. As end point lesions, γ–glutamyltransferase (GGT)‐positive enzyme‐altered foci were assayed at week 5. There was no significant effect of colchicine on numbers of foci. However, a significant, dose‐dependent increase in the area of GGT‐positive lesions in the groups treated with colchicine was observed. Bromodeoxyuridine labeling indices were higher in foci induced in colchicine‐treated rats than in the untreated rats. In a separate experiment, serum glutamic pyruvic transaminase was not increased significantly after DEN and colchicine treatment, and the mitotic index at 6 days after PH was increased in the liver of colchicine‐treated rats. These results suggest that the cell cycle disturbance induced by colchicine causes more pronounced selective growth of cells initiated by DEN and colchicine, and this experimental model may be useful for analyzing the mechanisms underlying that growth advantage and the effects of cell cycle abnormalities in liver carcinogenesis.