A methodology for the analysis of the preneoplastic antigen

Abstract

A highly sensitive assay for the epoxide hydrolase activity associated with the preneoplastic antigen (PNA) has been developed based on the synthesis of cis-stilbene oxide labeled with tritium at approximately 15 Ci/mmol. This assay allows the detection of elevated epoxide hydrolase activity in the serum of humans and rodents as well as in the culture medium bathing isolated hepatocytes. The integrity of the enzymatic assay was confirmed in rodents by precipitating the serum PNA activity using an antibody raised against the rat microsomal epoxide hydrolase. Methodology for the detection of PNA in serum will facilitate evaluation of this antigen as a marker for hepatic neoplasia in man and in experimental animals.

Discovery of Inhibitors of Soluble Epoxide Hydrolase: A Target with Multiple Potential Therapeutic Indications

“…17,18 In some pathological states the mEH dissociates from the membrane and appears in the blood where it is known as the preneoplatic antigen and is a marker for tissue damage including cancer. 19 Activity and polymorphisms of the enzyme have been associated with a variety of diseases, and this is a quite active area of research. 20 With regard to this review it is important to note that although the mEH and sEH have similar catalytic mechanisms and are members of the α/β-hydrolase fold family of proteins, their evolutionary paths diverged at the level of prokaryotes.…”

Development of monoclonal antibodies to human microsomal epoxide hydrolase and analysis of “preneoplastic antigen”-like molecules

“…(Okita et al , 1975) demonstrated that there is an antigen in preneoplastic foci in rat livers that is released into the blood, which was in later studies shown to be similar if not identical to the mEH (Levin et al , 1978). In later studies, a rapid radiochemical assay for the PNA was developed for human blood and shown to be associated with liver cancer, but it was also found to be associated with several other types of liver damage (Hammock et al , 1984). The AN antigen was purified from liver of a patient infected with HCV (Tohmatsu et al , 1985).…”

“…Although mEH is tightly associated with membranes in normal cells, the mEH is sometimes detected in the cytosol of neoplastic human livers and released into the blood (Gill et al , 1983). The appearance of mEH in the blood is also associated with other types of liver disease (Hammock et al , 1984). In hepatitis C infection, we have shown that the hepatitis C-associated antigen (AN antigen) appears in the early phase of the viral infection (Akatsuka et al , 1986b), which is followed by the development of the antibody in the acute phase of hepatitis (Akatsuka et al , 1986a).…”

Autoantibody response to microsomal epoxide hydrolase in hepatitis C and A

“…Following extensive studies by the Farber lab, Levin et al [40] demonstrated that the PNA is similar if not identical to the microsomal epoxide hydrolase. Later a rapid radiochemical assay for the PNA was developed for human blood and shown to be associated with liver cancer, but it was also found to be associated with several other types of liver damage [41]. Interestingly, another alpha/beta hydrolase fold enzyme -carboxylesterase -also has been shown to be released from hepatic endoplasmic reticulum and appears in the blood following liver injury [42].…”