Japanese Journal of Clinical Oncology Advance Access originally published online on August 16, 2008
Japanese Journal of Clinical Oncology 2008 38(9):604-610; doi:10.1093/jjco/hyn080
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© The Author (2008). Published by Oxford University Press. All rights reserved
Bile Duct-bound Growth of Precursor Cells of Preneoplastic Foci Inducible in the Initiation Stage of Rat Chemical Hepatocarcinogenesis by 2-Acetylaminofluorene
1 Department of Biomedical Sciences, Hirosaki University Graduate School of Health Sciences, Hirosaki, Aomori
2 Department of Signal Transduction, Research Institute of Microbial Disease, Osaka University, Osaka
3 Department of Neuropharmacology, Hokkaido University Graduate School of Medicine, Sapporo
4 Department of Pathologic Analysis, Aomori
5 Department of Pharmaceutical Science, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori, Japan
For reprints and all correspondence: Kimihiko Satoh, Department of Biomedical Sciences, Hirosaki University Graduate School of Health Sciences, Hon-Cho 66-1, Hirosaki 036-8564, Japan. E-mail: kisatoh{at}cc.hirosaki-u.ac.jp
Received April 7, 2008; accepted July 22, 2008
Background: We previously detected precursor cell populations of preneoplastic foci, GST-P+/GGT– and GST-P+/GGT+ minifoci, in rat liver in the initiation stage of chemical hepatocarcinogenesis, where GST-P and GGT represent glutathione S-transferase P-form and 
-glutamyltranspeptidase, respectively.
Methods: Sprague–Dawley male rats were fed a basal diet containing 2-acetylaminofluorene (0.02%) over 16 weeks. Precursor cells were detected by our sensitive staining method for GGT activity and immunocytochemical staining for GST-P.
Results: GST-P+/GGT– single cells were overproduced maximally in the animal liver after the 6 weeks followed by a gradual growth of GST-P+/GGT– and GST-P+/GGT+ minifoci, which were bound to bile ducts and ductules. GGT was expressed within GST-P+ minifoci gradually with time forming GGT+ lane-like structures. The bile duct binding and lane-like structure formation were prominent especially when minifoci-bearing rats were subjected to two-thirds partial hepatectomy.
Conclusions: A variety of precursor minifoci were noted to be selectively bound to bile ducts and ductules in rat liver, which may be of physiologic significance in excretion of carcinogens during initiation.
Key Words: hepatocarcinogenesis • tumor marker enzyme • -glutamyltranspeptidase • glutathione S-transferase • 2-acetylaminofluorene