DEVELOPMENT MONOCLONAL ANTIBODIES TO GOSSYPOL - PHASE I

COTTON PRODUCTION, A MAJOR BUSINESS IN THE UNITED STATES, OWES ABOUT 16% OF ITS AVERAGE VALUE TO COTTONSEED. ALTHOUGH USED FOR A VARIETY OF PURPOSES, OIL AND MEAL ACCOUNT FOR NEARLY 90% OF THE TOTAL VALUE OF THE COTTONSEED INDUSTRY. COTTONSEED MEAL IS THE SECOND LARGEST SOURCE OF NATURAL PROTEIN CONCENTRATE FOR LIVESTOCK IN THE UNITED STATES. ABOUT TWO-THIRDS OF THE COTTONSEED OIL PRODUCED IN THE UNITED STATES IS CONSUMED AS SALAD OR COOKING OIL WITH LESSER AMOUNTS USED IN BAKING FATS AND MARGARINE OILS. HOWEVER, COTTONSEED CONTAINS A YELLOW PIGMENT CALLED GOSSYPOL WHICH HAS CAUSED PROBLEMS FOR THE INDUSTRY FOR MANYYEARS. GOSSYPOL IS A HIGHLY REACTIVE PHENOLIC MOLECULE WHICH CAN COMPLEX WITH VARIOUS PROTEINS, AMINO ACIDS, ENZYMES AND MINERALS. ITS REPORTED BIOLOGICAL ACTIVITIES INCLUDE ANTIVIRAL, ANTIBACTERIAL, ANTITUMOR, ANTIOXIDANT, PESTICIDAL, TUMOR PROMOTOR, INTERFERON, AND ANTIFERTILITY EFFECTS. WHEN INGESTED IN EXCESSIVE AMOUNTS IN ITS FREE STATE, IT CAUSES ADVERSE EFFECTS ON DAIRY COW PRODUCTION. IT IS TOXIC TO NON-RUMINANT ANIMALS. TWO SPECIFIC AREAS CURRENTLY OF HIGH INTEREST ARE THE POTENTIAL USE OF GOSSYPOLAS AN ANTIFERTILITY AGENT FOR MALE CONTRACEPTION AND THE SELECTIVE REMOVAL OF GOSSYPOL FROM COTTONSEED FOODSTUFF BY A METHOD NOT DEPLETING IT OF ITS LYSINE CONTENT. THE PHASE I STUDY PROPOSED IS DIRECTED TOWARD ESTABLISHING "IN VITRO" HYBRIDOMA CULTURES WHICH SECRETE SPECIFIC MONOCLONAL ANTIBODIES TO GOSSYPOL. THE FEASIBILITY OF PRODUCING MONOCLONAL ANTIBODIES SPECIFIC TO THE DEXTRO- OR LEVO-ROTARYISOMERS OF GOSSYPOL WILL BE STUDIED. MONOCLONAL ANTIBODIES OF SUFFICIENT SPECIFICITY COULD BE USED EITHER AS TOOLS FOR (A) THE SEPARATION AND PURIFICATION OF THE INDIVIDUAL ISOMERFORMS FROM THE TAUTOMERIC MIXTURE OR (B) FOR THE REMOVAL OF FREE GOSSYPOL IN THE EARLY PROCESSING OF COTTONSEED FROM FOODSTUFFS. THESE APPLICATIONS WOULD BE OF BOTH CLINICAL AND INDUSTRIAL VALUE. THE DEVELOPMENT OF THE SEPARATION TECHNIQUES WOULD BE THE SUBJECT OF PHASE II STUDIES. EACH PHASE I ASPECT (A,B) WOULD LEND ITSELF TO AN INDIVIDUAL PHASE II STUDY. THE FIRST SPECIFIC AREA OF RESEARCH (A) ADDRESSES THE PROGRAM DESCRIPTION IN THE PHS OMNIBUS SOLICITATION FOR CONTRACEPTIVE DEVELOPMENT UNDER THE NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT. THE SECOND AREA (B) ADDRESSES THAT FOR THE BUREAU OF FOODS OF THE FOOD AND DRUG ADMINISTRATION AS RELATED TO THE DETECTION, PREVENTION, AND CONTROL OF CONTAMINATION THAT MAY CAUSE INJURY.