The expression of cytochrome P-450, epoxide hydrolase, and glutathione S-transferase in hepatocellular carcinoma.
BACKGROUND
Cytochrome P-450, epoxide hydrolase, and glutathione S-transferase (GST) all play a key role in the metabolism of chemical carcinogens, mutagens, and various anti-cancer drugs. All these functionally associated enzymes might be involved in both the development of hepatocellular carcinoma and in determining the anti-cancer drug sensitivity of such tumors.


METHODS
The expression of two forms of cytochrome P-450 (P-450 IA and P-450 IIIA), microsomal epoxide hydrolase, and three classes of cytosolic GST (alpha, mu, and pi) have been studied immunohistochemically in human hepatocellular carcinoma.


RESULTS
The hepatocellular carcinomas were characterized by a consistently high expression of epoxide hydrolase and variable expression of the cytochromes P-450 and GST. Cytochrome P-450 IA and IIIA stained in 64.5% and 41.9% of the 31 hepatocellular carcinomas studied, respectively. Epoxide hydrolase was present in all tumors, and GST types alpha, pi, and mu were identified in 48.4%, 38.7%, and 74.2% of the hepatocellular carcinomas, respectively.


CONCLUSIONS
This study showed that the expression of xenobiotic-metabolizing enzymes in hepatocellular carcinoma is complex and the presence of different xenobiotic enzymes in hepatocellular carcinoma may contribute to the intrinsic drug resistance of these tumors.
Department of Pathology, University of Aberdeen, Foresterhill, UK.
G I
GI
Murray
P J
PJ
Paterson
R J
RJ
Weaver
S W
SW
Ewen
W T
WT
Melvin
M D
MD
Burke
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001189:Aryl Hydrocarbon Hydroxylases; D006528:Carcinoma, Hepatocellular / Q000201:enzymology*; D019363:Cytochrome P-450 CYP1A1; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000032:analysis*; D003600:Cytosol / Q000201:enzymology; D004851:Epoxide Hydrolases / Q000032:analysis*; D005260:Female; D005982:Glutathione Transferase / Q000032:analysis*; D006801:Humans; D008099:Liver / Q000201:enzymology*; D008113:Liver Neoplasms / Q000201:enzymology*; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology; D008875:Middle Aged; D010088:Oxidoreductases / Q000032:analysis*; D010089:Oxidoreductases, N-Demethylating / Q000032:analysis*
D003577:Cytochrome P-450 Enzyme System; D010088:Oxidoreductases; D001189:Aryl Hydrocarbon Hydroxylases; D019363:Cytochrome P-450 CYP1A1; D051544:Cytochrome P-450 CYP3A; D010089:Oxidoreductases, N-Demethylating; D005982:Glutathione Transferase; D004851:Epoxide Hydrolases