CHANGES IN CATALASE AND GLUCOSE-6-PHOSPHATASE DISTRIBUTION PATTERNS WITHIN OVAL CELL COMPARTMENT AS POSSIBLE DIFFERENTIATION MARKERS DURINGVIRAL HEPATOCARCINOGENESIS IN WOODCHUCKS
S. Radaeva et P. Bannasch, CHANGES IN CATALASE AND GLUCOSE-6-PHOSPHATASE DISTRIBUTION PATTERNS WITHIN OVAL CELL COMPARTMENT AS POSSIBLE DIFFERENTIATION MARKERS DURINGVIRAL HEPATOCARCINOGENESIS IN WOODCHUCKS, Differentiation, 60(3), 1996, pp. 169-178
Cytochemical analysis at the ultrastructural level was performed to ch
aracterize expression of catalase and glucose-6-phosphatase (G6Pase) a
ctivity as possible differentiation markers in oval cells proliferatin
g during hepatocarcinogenesis induced in woodchucks by chronic infecti
on with the woodchuck hepatitis virus (WHV) and additional treatment w
ith aflatoxin B-1 (AFB(1)). Oval cells from WHV-carriers treated with
AFB(1) showed two types of catalase-positive organelles: 1) microperox
isomes appearing as small strongly osmiophilic bodies corresponding to
those present in biliary cells from control woodchucks, 2) peroxisome
s with a hepatic staining pattern resembling those of mature hepatocyt
es but lacking a nucleoid. While in oval cells penetrating into the pa
renchyma a catalase-positive reaction product was restricted to rare m
icroperoxisomes, in close vicinity to the portal tract about 30% of th
e oval cells produced peroxisomes with a hepatic staining pattern, ind
icating the existence of two different populations within the oval cel
l compartment. Peroxisomes with a hepatic staining pattern formed clus
ters and exhibited pleomorphism with marked variation in shape and siz
e, the size sometimes coming up to that of normal hepatocellular perox
isomes. Serial sections revealed the complex organization of these per
oxisomes. They consisted of several interconnected segments forming a
peroxisomal reticulum. These findings are consistent with the hypothes
is that a subpopulation of oval cells represents committed precursor c
ells capable of differentiating into hepatocytes. Activity of G6Pase w
as not demonstrable in this subpopulation of oval cells and became pos
itive only in transitional cells. Differential expression of catalase
and G6Pase activity in a stepwise fashion within the oval cell compart
ment appear to mark differentiation of oval cells into hepatocytes. Th
us, elevated expression of catalase may be a useful early marker for t
he distinction of different subpopulations of oval cells committed to
hepatic cell lineages before definitely changing their phenotype, wher
eas expression of G6Pase activity seems to begin later, accompanying m
orphological changes towards the phenotype of mature hepatocytes.