Prevention of benzene (or radiation) induced acute myeloid leukemia (or bone marrow failure) by myeloperoxidase inhibitor

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While it is known that benzene induces myeloid leukemia in humans, the mechanism has yet to be clarified. Previously, we suggested that myeloperoxidase (MPO) was the key enzyme because it promotes generation of powerful oxidant hypochlorous acid which reacting with DNA. In our study, using a whole-human-genome oligonucleotide microarray, we analyzed the genome-wide expression profiles of HL60 human promyelocytic cell lines exposed to 1,2,4-benzenetriol (BT) with or without MPO inhibition. The microarray analysis revealed that 4h exposure to BT changed the expressionin HL60 cells of 1213 genes associated with transcription, RNA metabolic processes, immuneresponse, apoptosis, cell death, and biosynthetic processes, and that these changes were dramatically lessened by MPO-specific inhibition. Gene expression profiles along with GO and KEGG pathway annotation analysis suggest that there maybe a role for MPO as an examination marker or in prophylaxis forchemical carcinogenesis.