Enzymatic detection of precursor cell populations of preneoplastic foci positive for gamma-glutamyltranspeptidase in rat liver.
An improved staining method for gamma-glutamyltranspeptidase (GGT) was developed using Vibratome-prepared microslices. Microscopic precursor cell populations of preneoplastic foci positive for the marker enzyme were detectable sequentially in rat liver by tracing back from 5 to 1 week after carcinogen injection in a hepatocarcinogenesis model. Mirror-image comparisons of serial sections stained for GGT activity and immunocytochemically stained for GST-P (glutathione S-transferase P-form) revealed that GGT expression was confined within GST-P(+) cell populations (GST-P(+) minifoci), which are induced in the periportal area (zone 1) of the liver. GGT expression level differed from one minifocus to another, and the larger the GST-P(+) focus, the stronger was the GGT expression in it, indicating that GST-P(+)/GGT(-) phenotypes are convertible into proliferating GST-P(+)/GGT(+) ones. Our results suggest that there are at least 2 closely related precursors, GST-P(+)/GGT(-) and GST-P(+)/GGT(+) phenotypes, of preneoplastic foci in rat chemical hepatocarcinogenesis.
Satoh
Kimihiko
K
Department of Organic Function, Hirosaki University, School of Health Science, Hirosaki, Japan. kisatoh@cc.hirosaki-u.ac.jp
Takahashi
Gen
G
Miura
Tomisato
T
Hayakari
Makoto
M
Hatayama
Ichiro
I
D000818:Animals; D014408:Biomarkers, Tumor / Q000032:analysis*; D002273:Carcinogens / Q000008:administration & dosage; D002471:Cell Transformation, Neoplastic; D004195:Disease Models, Animal; D005982:Glutathione Transferase / Q000032:analysis; D007150:Immunohistochemistry; D008099:Liver / Q000201:enzymology; D008113:Liver Neoplasms / Q000503:physiopathology*; D008297:Male; D010641:Phenotype; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D005723:gamma-Glutamyltransferase / Q000032:analysis*
D014408:Biomarkers, Tumor; D002273:Carcinogens; D005723:gamma-Glutamyltransferase; D005982:Glutathione Transferase