THE DEVELOPMENT OF A SENSITIVE, RAPID, AND RELATIVELY INEXPENSIVE SERUM ASSAY FOR SPECIFIC FORMS OF CANCER WOULD BE INVALUABLE FOR THE EARLY DIAGNOSIS OF THE CANCER, ITS SUBSEQUENT TREATMENT, AND STUDIES ON THE ETIOLOGY AND EPIDEMIOLOGY OF THE DISEASE.

THE DEVELOPMENT OF A SENSITIVE, RAPID, AND RELATIVELY INEXPENSIVE SERUM ASSAY FOR SPECIFIC FORMS OF CANCER WOULD BE INVALUABLE FOR THE EARLY DIAGNOSIS OF THE CANCER, ITS SUBSEQUENT TREATMENT, AND STUDIES ON THE ETIOLOGY AND EPIDEMIOLOGY OF THE DISEASE. WHILE NOT A DIAGNOSTIC PANACEA, THE SERUM ASSAY COULD QUICKEN DIAGNOSIS AND AID IN FOLLOW-UP ON THE PROGRESSION OR REGRESSION OF THE NEOPLASM. IN THIS PROPOSAL WE PLAN TO DEVELOP AN IMMUNOCHEMICAL ASSAY FOR HUMAN SERUM EPOXIDE HYDROLASE-PRENEOPLASTIC ANTIGEN IN ORDER TO FACILITATE STUDIES ON THIS ASSAY AS A SPECIFIC TEST FOR HEPATO-CELLULAR CARCINOMA IN HUMANS (PHASE I). THE NUMBER ONE CAUSE OF DEATH FROM CANCER, LIVER CANCER HAS AN ETIOLOGICALLY PREDISPOSING POPULATION OF MILLIONS WHO SUFFER FROM HEPATITIS B, CIRRHOSIS, AND OTHER CHRONIC LIVER DISEASES. BASED ON STUDIES IN FARBER'S GRIFFIN'S AND LEVIN'S LABORATORIES A PROTEIN EH-PNA (EPOXIDE HYDROLASE-PRENEOPLASTIC ANTIGEN) HAS BEEN DESCRIBED WHICH IS RELEASED FROM ITS MEMBRANOUS ENVIRONMENT SPECIALLY IN PRENEOPLASTIC AND NEOPLASTIC LIVER CELLS OF RODENTS. A SENSITIVE RADIOCHEMICAL ASSAY FOR EH-PNA DEVELOPED IN HAMMOCK'S LABORATORY (UNIVERSITY OF CALIFORNIA) HAS NOW PROVIDED EVIDENCE THAT ELEVATED EH-PNA APPEARS IN THE SERUM OF PATIENTS WITH HEPATO-CELLULAR CARCINOMA. USING ANTIBODIES AGAINST RAT EPOXIDE HYDROLASE A RAPID ENZYME-LINKED-IMMUNOABSORBENT-ASSAY (ELISA) HAS BEEN DEVELOPED DEMONSTRATING THE APPLICABILITY OF THIS TECHNIQUE FOR MEASURING EH-PNA. THE PURPOSE OF PHASE I OF THIS PROPOSAL IS TO DEVELOP AN IMMUNOCHEMICAL ASSAY FOR EH-PNA IN HUMAN SERUM. THIS ASSAY SHOULD BE OF PRIMARY INTEREST TO THE DIVISION OF CANCER BIOLOGY AND DIAGNOSIS, NATIONAL CANCER INSTITUTE. IT WILL INVOLVE WORK UNDER A LICENSING AGREEMENT ON AN INVENTION BY THE UNIVERSITY OF CALIFORNIA (THE MEASUREMENT OF SERUM EH-PNA) FOR WHICH A PATENT APPLICATION HAS BEEN MADE. THIS WILL ALLOW A SMALL BUSINESS IN CALIFORNIA TO PURSUE SPECIFIC RESEARCH THAT MAY LEAD EVENTUALLY TO THE RIGHTS FOR PRODUCTION AND MARKETING OF THE ASSAY KIT. COLLABORATION WITH THE UNIVERSITY OF CALIFORNIA WILL OCCUR ON SCIENTIFIC ASPECTS OF THE ASSAY. THE SPECIFIC AIMS FOR PHASE I ARE: 1) TO ISOLATE EH-PNA FROM LIVER MICROZOMES OF A PRIMATE, 2) TO USE THE ISOLATED EH-PNA AS AN ANTIGEN TO INDUCE ANTISERA IN GOATS AND RABBITS, 3) TO MAKE THE ANTISERA (IGG FRACTION) MONO-SPECIFIC FOR EH-PNA, AND 4) TO DEVELOP AN ELISA FOR EH-PNA APPLICABLE TO HUMAN SERA. THE KIT WOULD THEN BE DISTRIBUTED FOR USE IN STUDIES ON THE EFFICIENCY OF THE ASSAY WHICH WILL PROVIDE THE BASIS FOR PHASE II OF THIS PROJECT.