Bile duct-bound growth of precursor cells of preneoplastic foci inducible in the initiation stage of rat chemical hepatocarcinogenesis by 2-acetylaminofluorene.
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 gamma-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.
Satoh
Kimihiko
K
Department of Biomedical Sciences, Hirosaki University Graduate School of Health Sciences, Hirosaki 036-8564, Japan. kisatoh@cc.hirosaki-u.ac.jp
Yamakawa
Daishi
D
Sugio
Hideaki
H
Kida
Kazuyuki
K
Sato
Tatsusuke
T
Hosoi
Kazuhiro
K
Hayakari
Makoto
M
D015073:2-Acetylaminofluorene; D000818:Animals; D001652:Bile Ducts / Q000201:enzymology* / Q000473:pathology; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D051549:Glutathione S-Transferase pi / Q000096:biosynthesis*; D008114:Liver Neoplasms, Experimental / Q000201:enzymology* / Q000473:pathology; D008297:Male; D011230:Precancerous Conditions / Q000201:enzymology* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D005723:gamma-Glutamyltransferase / Q000096:biosynthesis*
D014408:Biomarkers, Tumor; D015073:2-Acetylaminofluorene; D005723:gamma-Glutamyltransferase; D051549:Glutathione S-Transferase pi; C496558:Gstp1 protein, rat