The expression of cytochrome P-450, epoxide hydrolase, and glutathione s-transferase in hepatocellular carcinoma

Abstract

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. Cancer 1993; 71:36‐43.

Glutathione S Transferase Theta 1 Gene (GSTT1) Null Genotype Is Associated with an Increased Risk for Acquired Aplastic Anemia in Children

“…The wild-type C1/C1 alleles were comparable in 83 of 91 (91%) patients with AA and 222 of 235 (94.5%) controls (NS). The respective prevalence in healthy controls was comparable to data from other studies that analyzed Caucasian patients (20,21,43). These data exhibit no association of p450-cyp2E1 polymorphism with a risk for AA in children.…”

“…A null genotype is characterized by the absence of the respective GST protein (38). The GSTM1 null genotype has been shown to be associated with an increased risk of smoke-induced cancers (39 -41), breast cancers (42), and hepatocellular carcinoma (43,44). The GSTT1 null genotype has been shown to be associated with an increased risk for MDS (44 -46).…”

Expression of cytochrome P450 1A1/2 and 3A4 in liver tissues of hepatocellular carcinoma cases and controls from Taiwan and their relationship to hepatitis B virus and aflatoxin B1-and 4-aminobiphenyl-DNA adducts

“…Tumour and adjacent non-tumour tissue of HCC cases also showed interindividual variation in staining intensity. Variable expression of both CYP1A and 3A in primary malignant liver tumours by Western blot (Kirby et al 1993), immunohistochemistry (Murray et al 1993) and in situ hybridization (McKinnon et al 1991) has been observed previously.…”

“…The staining pattern observed in this study, a diffuse cytoplasmic immunoreactivity for tumour tissues, was similar to that found in a previous study (Murray et al 1993). Both tumour and adjacent non-tumour tissues showed loss of normal lobular structure.…”

“…These results suggest that CYP3A4 may be more important in DNA adduct formation in tissues from cases than controls. A single previous study examined CYP3A4 expression in HCC samples and found detectable levels in 12 (38.7 %) (Murray et al 1993).…”