Benzene, a major industrial chemical, environmental pollutant and tobacco smoke constituent has been shown to cause aplastic anemia and acute myeloid leukemia in man. Epidemiological studies have demonstrated an association between smoking and myeloid leukemia. Since benzene and some of its metabolites are present in tobacco smoke in significant amounts, we hypothesize that benzene is a likely contributor to the increased risk of smokers for leukemia. Therefore, we plan to develop and validate assays which will be used as dosimeters of benzene exposure in smokers. These assays will be based on a) benzene-derived globin adducts; b) blood serum albumin adducts; c) urinary amino acid adducts; d) urinary muconic acid.
The specific aims of this study are: 1. to characterize benzene- derived major globin (Gb) and serum albumin (SA) adducts in mice and rats, and compare protein adducts obtained from rodent blood with those that are formed from human blood in vitro. 2. to assess the dose- response relationship between [14C]benzene exposure, formation of protein adducts, and formation of urinary metabolites. 3. to assess the stability of each adduct and its accumulation as a result of chronic exposure. 4. to develop sensitive methods for quantitation of urinary metabolites. 5. to develop methods with increased sensitivity of detection for the major benzene-derived protein adduct found in humans. (Specific Aim 1) 6. to assess the dose-response relationship between number of cigarettes smoked, formation of the blood protein adducts, and formation of the urinary metabolites. This study, in combination with epidemiological studies, will clarify the relationship between benzene exposure from cigarette smoke and leukemia cases in smokers and serve to improve risk assessment.
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