Serum epoxide hydrolase (preneoplastic antigen) in human and experimental liver injury

David E. Moody, Dana N. Loury, Brucc D. Hammock, Boris H. Ruebner, John M. Cullen, James H. Hillman, David W. Hillman, M. Sambasiva Rao, W. Thomas London, Hei Won L Hann, Irving Millman, Martin J. Griffin

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Abstract

Reports of an increase in a serum epoxide hydrolase (sEH), immunochemically related to microsomal EH in humans and rats with hepatocellular carcinoma (HCC), suggested its use as a serum marker for this disease. We have now measured sEH levels (as either immunochemically determined content or enzyme activity) in a number of human and experimental models of liver disease. sEH was elevated above the normal range in at least 50% of individuals with HCC, including: 3 of 6 northern Californians; 4 of 7 Koreans with hepatitis B-associated HCC; hepatitis B-associated HCC in woodchucks; and male rats receiving chronic treatment with aflatoxin B, or ciprofibrate. sEH was rarely elevated in other forms of chronic liver disease. Only 2 of 9 Koreans with hepatitis B-associated cirrhosis, 1 of 8 carriers, but none with chronic active hepatitis or infection with no apparent liver disease had elevated sEH. In addition, no elevations were found in woodchucks with noncancerous viral hepatitis. In aflatoxin B1- and M1-treatcd rats sEH was not elevated in those with only hyperplastic foci or hepatocellular adenomas, and in two rat initiation-promotion protocols sEH was elevated only in those rats which received the entire set of treatments. sEH was also increased during acute hepalotoxicity in rats treated with CCl4 or 1,2-dibromo-3-chloropropane. The mechanism of increase in sEH during hepatocarcinogenesis appears to be different from that of other markers of HCC, for in the Korean patients, there was no correlation between sEH concentrations and those of α-fetoprotein or ferritin, nor was there a correlation with α-fetoprotein concentrations in the aflatoxin-treated rats. Furthermore, the increase in sEH does not correlate with induction of microsomal EH in the liver of experimental animals. Studies to date indicate that sEH is selective for HCC and severe hepatonecrotic injury, and may be of some use in the diagnosis of HCC, particularly as a complement to other serum markers.

Original languageEnglish (US)
Pages (from-to)395-403
Number of pages9
JournalCancer Epidemiology Biomarkers and Prevention
Volume1
Issue number5
StatePublished - 1992

ASJC Scopus subject areas

  • Epidemiology
  • Oncology

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    Moody, D. E., Loury, D. N., Hammock, B. D., Ruebner, B. H., Cullen, J. M., Hillman, J. H., Hillman, D. W., Rao, M. S., London, W. T., Hann, H. W. L., Millman, I., & Griffin, M. J. (1992). Serum epoxide hydrolase (preneoplastic antigen) in human and experimental liver injury. Cancer Epidemiology Biomarkers and Prevention, 1(5), 395-403.