IMMUNOASSAYS FOR MUTAGENIC AND CARCINOGENIC ADDUCTS IN HUMAN DNA

DIFUNCTIONAL CARBONYL COMPOUNDS ARE TOXIC, MUTAGENIC, AND CARCINOGENIC AND ARE UBIQUITOUS CONTAMINANTS OF THE HUMAN ENVIRONMENT. THE SIMPLEST EXAMPLES OF SUCH COMPOUNDS ARE MALONDIALDEHYDE, ACROLEIN, AND METHYL GLYOXAL. MALONDIALDEHYDE IS A PRODUCT OF LIPID PEROXIDATION AND PROSTAGLANDIN BIOSYNTHESIS AND IS PRESENT IN VIRTUALLY ALL MAMMALIAN TISSUES. METHYL GLYOXAL IS ALSO A NATURAL PRODUCTAND IS PRESENT IN FRESHLY ROASTED COFFEE. ACROLEIN IS A MAJOR INDUSTRIAL STARTING MATERIAL AND IS PRESENT IN CIGARETTE SMOKE. ALL OF THESE COMPOUNDS ARE MUTAGENIC, AND METHYL GLYOXAL INDUCES SUBCUTANEOUS TUMORS WHEN INJECTED IN MICE. THE EXTENT TO WHICH DIFUNCTIONAL CARBONYL COMPOUNDS CONTRIBUTE TO HUMAN CANCER IS UNCERTAIN, BUT THERE CAN BE LITTLE DOUBT THAT EXPOSURE TO THESE COMPOUNDS IS CONSIDERABLE. WHILE IT IS THOUGHT THAT THESE COMPOUNDS EXERT THEIR MUTAGENIC AND CARCINOGENIC EFFECTS BY FORMING ADDUCTS WITH DNA, METHODS FOR ACCURATE DETERMINATION OF THESE ADDUCTS ARE NOT AVAILABLE. THE LONG-TERM GOALS OF THIS PROJECT ARE THE DEVELOPMENT OF MONOCLONAL ANTIBODIES SPECIFIC FOR THE MAJOR NUCLEIC ACID ADDUCTS OF THESE DIFUNCTIONAL CARBONYL COMPOUNDS, FOR USE IN ENZYME-LINKED IMMUNOSORBENT ASSAYS AND IN ASSAYS OF SPREAD DNA AND DNA IN NUCLEI. THESE ASSAYS WILL BE DEVELOPED FOR USE IN CLINICAL AND RESEARCH MONITORING OF LEVELS OF THESE ADDUCTS IN HUMAN DNA SAMPLES.