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.
Murray
G I
GI
Department of Pathology, University of Aberdeen, Foresterhill, UK.
Paterson
P J
PJ
Weaver
R J
RJ
Ewen
S W
SW
Melvin
W T
WT
Burke
M D
MD
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