BIOLOGICAL MARKERS OF CHRONIC EXCESS ETHANOL CONSUMPTION

点击翻译按钮获取中文摘要

The aim of this proposal is to develop a gas-chromatographic mass-spectrometric (GC/MS) procedure and a novel screening blood test for measurement of ethanol and acetaldehyde (ALD) conjugates in blood and to establish the feasibility of their use as markers for ethanol consumption. Since proteins, especially red cell proteins, have a long life span, measurement of the accumulated hemoglobin-ALD-adducts have been proposed as biological markers. Other potential markers are ethyl esters of fatty acids, which are found in human tissues. Recently, ethanol conjugates were detected in urine and blood of abstaining alcoholics. It is hypothesized the concurrent measurements of both ethanol and ALD conjugates in blood may serve as the most direct and long-lasting biological markers for ethanol consumption. The present GC/MS procedure for ethanol conjugates can be further developed for simultaneous measurements of low concentration ALD conjugates. In the presence of sodium borodeuteride, a reducing agent, ALD produced after acid hydrolysis should give deuterated ethanol which could be determined by GC/MS. This method will be used to test the feasibility of using both ethanol and ALD conjugates as biological markers of chronic excessive ethanol consumption, by re-analysing a special collection of blood samples from alcoholics and controls. These samples have been collected by Dr. Israel, head of biochemical research, clinical Institute of The Addiction Research Foundation of Ontario for his development of an enzyme-linked immunosorbent assay (ELISA) against hemoglobin-ALD-adducts. The GC/MS procedure will also be used to develop a novel blood test for screening based on radio albumin binding of acetaldehyde and ethanol.