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[Enzyme alterations during chemical hepatocarcinogenesis]
Gan to Kagaku Ryoho. Cancer & Chemotherapy
|June 1, 1987
Summary
Glutathione S-transferase pi (GST-P) is a novel marker for rat chemical hepatocarcinogenesis. This enzyme significantly increases in preneoplastic hepatic lesions, aiding in early detection.
Area of Science:
- Biochemistry
- Oncology
- Enzymology
Context:
- Hepatocarcinogenesis involves biochemical changes in enzyme phenotypes.
- Enzyme isoforms serve as markers for neoplastic hepatic tissues.
- Drug-metabolizing enzymes, particularly Phase I and Phase II, exhibit altered expression during carcinogenesis.
Purpose:
- To identify novel biochemical markers for rat chemical hepatocarcinogenesis.
- To characterize a new neutral glutathione S-transferase (GST) form, GST-P, as a potential marker.
- To investigate the expression patterns of GST-P in preneoplastic and neoplastic hepatic lesions.
Summary:
- A new neutral GST form, GST-P (pI 7.0), was identified as a sensitive marker for rat chemical hepatocarcinogenesis.
- GST-P is a homodimer with a unique subunit structure and differs immunochemically from other GST forms.
- GST-P levels are low in normal liver but significantly elevated (ten-fold) in hepatocyte nodules and hepatomas induced by various carcinogens.
- Immunohistochemical analysis reveals GST-P localization in hepatocyte nodules and early GST-positive foci, detectable with anti-GST-P antibodies.
- Importantly, GST-P is not expressed in hepatic lesions induced by non-genotoxic carcinogens like peroxisome-proliferating agents, distinguishing it from gamma-glutamyl transpeptidase (gamma-GTP).
Impact:
- GST-P serves as a highly specific and sensitive marker for early detection of chemically induced preneoplastic and neoplastic hepatic lesions in rats.
- The distinct expression pattern of GST-P, especially its absence in lesions from non-genotoxic carcinogens, aids in differentiating carcinogenic mechanisms.
- This finding contributes to a better understanding of enzyme alterations during hepatocarcinogenesis and provides a valuable tool for toxicological research and chemoprevention studies.