Benzene is an ubiquitous environmental pollutant and continues to be used as a solvent in developing countries. Benzene is an established cause of human leukemia, but the risk it poses at different exposure levels is highly controversial. The mechanism by which benzene exerts its toxic effects also remains unclear. Through their studies, the investigators hope to provide insight into the mechanism of benzene-induced leukemogenesis and to develop clinically-relevant biomarkers of exposure and genotoxicity for use in epidemiological investigations of human exposure to benzene and other potential leukemogens. This project has provided new information regarding benzene-induced leukemogenesis by analyzing the blood cells of exposed workers using fluorescence in situ hybridization (FISH). To date, they have investigated aneuploidy of four chromosomes, 7, 8, 9 and 21, and translocations between 8 and 21. They propose to continue and expand this analysis to 10 chromosomes for aneuploidy and 5 or more translocations of relevance to leukemogenesis. In total, 94 individuals with current or past exposure to benzene will be studied along with 72 matched controls. The biologic samples have already been collected and the exposure assessment has been validated by measurement of urinary metabolites and hematotoxicity. This study, therefore, provides a unique opportunity to gain insight into benzene-induced leukemia and develop clinically-relevant biomarkers in a cost-efficient manner. The data obtained thus far suggest that lower exposures to benzene have a selective aneuploidy-inducing effect on chromosome 7. The investigators propose to expand upon and confirm this finding by analyzing chromosomes 6, 7, and 11 in interphase cells and 1, 5 and 7 in metaphase spreads using FISH. Alterations in 5q and 7q will also be investigated since changes at these sites are commonly detected in human leukemias, especially those related to benzene or other solvent exposure. The data obtained to date also demonstrate that benzene exposure increases the frequency of translocations between chromosomes 8 and 21, t(8;21), which are frequently observed in acute myelogenous leukemia. This work will be expanded upon by using chromosome painting to determine if benzene produces other translocations of importance in leukemia, e.g., t(9;22) and t(4;11), and by examining the possibility of using RT-PCR to detect t(8;21) and other translocations.
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