Epoxide hydrolase: a marker for experimental hepatocarcinogenesis

Area of Science:

• Biochemistry
• Toxicology
• Oncology

Background:

• Chemical hepatocarcinogenesis in rats involves preneoplastic stages like hyperplastic nodules preceding hepatoma development.
• Epoxide hydrolase, an endoplasmic reticulum enzyme, is significantly upregulated in hyperplastic nodules and hepatomas.

Purpose of the Study:

• To investigate the presence of circulating epoxide hydrolase immunodeterminants in rats with chemically induced liver tumors.
• To evaluate epoxide hydrolase as a potential biomarker for preneoplastic and neoplastic liver lesions.

Main Methods:

• Purification of rat liver epoxide hydrolase and preparation of rabbit antiserum.
• Development and application of enzyme-linked immunosorbent assay (ELISA) and passive hemagglutination inhibition assay.

Main Results:

• Significant levels of circulating microsomal epoxide hydrolase antigen were found in all tested rats with hepatomas (0.01–2.50 µg/ml).
• Rats with hyperplastic nodules also showed significantly elevated antigen levels, while control rats had undetectable levels (<0.004 µg/ml).
• Passive hemagglutination inhibition assay confirmed the presence of epoxide hydrolase immunodeterminants in hepatoma-bearing rat sera.

Conclusions:

• Epoxide hydrolase, induced during chemical hepatocarcinogenesis, circulates in the blood of tumor-bearing rats.
• This circulating antigen, termed preneoplastic antigen, serves as a potential biomarker for experimental liver cancer detection.