BACKGROUND: Although benzene is known to be myelotoxic and to cause myeloid leukemia in humans, the mechanism has not been elucidated.
OBJECTIVES: We focused on 1,2,4-benzenetriol (BT), a benzene metabolite that generates reactive oxygen species (ROS) by autoxidation, to investigate the toxicity of benzene leading to leukemogenesis.
METHODS: After exposing HL-60 human myeloid cells to BT, we investigated the cellular effects, including apoptosis, ROS generation, DNA damage, and protein damage. We also investigated how the cellular effects of BT were modified by hydrogen peroxide (H2O2) scavenger catalase, hypochlorous acid (HOCl) scavenger methionine, and 4-aminobenzoic acid hydrazide (ABAH), a myeloperoxidase (MPO)-specific inhibitor.
RESULTS: BT increased the levels of apoptosis and ROS, including superoxide (O2•-), H2O2, HOCl, and the hydroxyl radical (•OH). Catalase, ABAH, and methionine each inhibited the increased apoptosis caused by BT, and catalase and ABAH inhibited increases in HOCl and •OH. Although BT exposure increased halogenated DNA, this increase was inhibited by catalase, methionine, and ABAH. BT exposure also increased the amount of halogenated tyrosines; however, it did not increase 8-oxo-deoxyguanosine.
CONCLUSIONS: We suggest that BT increases H2O2 intracellularly; this H2O2 is metabolized to HOCl by MPO, and this HOCl results in possibly cytotoxic binding of chlorine to DNA. Because myeloid cells copiously express MPO and because halogenated DNA may induce both genetic and epigenetic changes that contribute to carcinogenesis, halogenative stress may account for benzene-induced bone marrow disorders and myeloid leukemia.

[Untagged]
━ Inclusion
━ ━ 1,3-butadiene
━ ━ ━ Mouse
━ ━ ━ ━ in vivo
━ ━ ━ ━ ━ DNA methylation
━ ━ ━ ━ ━ Histone modification
━ ━ 4-Aminobiphenyl
━ ━ ━ Human
━ ━ ━ ━ in vitro
━ ━ ━ ━ ━ microRNA
━ ━ ━ ━ ━ Histone modification
━ ━ Aflatoxins
━ ━ ━ Human
━ ━ ━ ━ in vitro
━ ━ ━ ━ ━ DNA methylation
━ ━ ━ ━ ━ microRNA
━ ━ ━ ━ ━ lncRNA
━ ━ ━ ━ in vivo
━ ━ ━ ━ ━ DNA methylation
━ ━ ━ ━ ━ microRNA
━ ━ ━ Mouse
━ ━ ━ ━ in vitro
━ ━ ━ ━ ━ microRNA
━ ━ ━ ━ in vivo
━ ━ ━ ━ ━ DNA methylation
━ ━ ━ ━ ━ Histone modification
━ ━ ━ Rat
━ ━ ━ ━ in vivo
━ ━ ━ ━ ━ DNA methylation
━ ━ ━ ━ ━ microRNA
━ ━ ━ Other
━ ━ ━ ━ in vitro
━ ━ ━ ━ ━ DNA methylation
━ ━ ━ ━ ━ Histone modification
━ ━ ━ ━ in vivo
━ ━ ━ ━ ━ DNA methylation
━ ━ ━ ━ ━ Histone modification
━ ━ Benzene
━ ━ ━ Human
━ ━ ━ ━ in vitro
━ ━ ━ ━ ━ DNA methylation
━ ━ ━ ━ in vivo
━ ━ ━ ━ ━ DNA methylation
━ ━ ━ ━ ━ Histone modification
━ ━ ━ ━ ━ microRNA
━ ━ ━ ━ ━ lncRNA
━ ━ ━ Mouse
━ ━ ━ ━ in vitro
━ ━ ━ ━ ━ DNA methylation
━ ━ ━ ━ in vivo
━ ━ ━ ━ ━ DNA methylation
━ ━ ━ ━ ━ Histone modification
━ ━ ━ ━ ━ microRNA
━ ━ ━ Rat
━ ━ ━ ━ in vitro
━ ━ ━ ━ ━ DNA methylation
━ ━ ━ ━ ━ Histone modification
━ ━ ━ ━ in vivo
━ ━ ━ ━ ━ DNA methylation
━ ━ Benzidine
━ ━ ━ Mouse
━ ━ ━ ━ in vivo
━ ━ ━ ━ ━ DNA methylation
━ ━ Benzo[a]pyrene
━ ━ ━ Human
━ ━ ━ ━ in vitro
━ ━ ━ ━ ━ DNA methylation
━ ━ ━ ━ ━ Histone modification
━ ━ ━ ━ ━ microRNA
━ ━ ━ ━ ━ lncRNA
━ ━ ━ ━ in vivo
━ ━ ━ ━ ━ DNA methylation
━ ━ ━ ━ ━ microRNA
━ ━ ━ Mouse
━ ━ ━ ━ in vitro
━ ━ ━ ━ ━ DNA methylation
━ ━ ━ ━ ━ Histone modification
━ ━ ━ ━ ━ microRNA
━ ━ ━ ━ in vivo
━ ━ ━ ━ ━ Histone modification
━ ━ ━ ━ ━ DNA methylation
━ ━ ━ ━ ━ microRNA
━ ━ ━ ━ ━ lncRNA
━ ━ ━ Rat
━ ━ ━ ━ in vivo
━ ━ ━ ━ ━ Histone modification
━ ━ ━ ━ ━ microRNA
━ ━ ━ Other
━ ━ ━ ━ in vitro
━ ━ ━ ━ ━ DNA methylation
━ ━ ━ ━ ━ Histone modification
━ ━ ━ ━ in vivo
━ ━ ━ ━ ━ DNA methylation
━ ━ Coke production
━ ━ ━ Human
━ ━ ━ ━ in vivo
━ ━ ━ ━ ━ microRNA
━ ━ ━ ━ ━ DNA methylation
━ ━ Formaldehyde
━ ━ ━ Human
━ ━ ━ ━ in vitro
━ ━ ━ ━ ━ DNA methylation
━ ━ ━ ━ ━ Histone modification
━ ━ ━ ━ ━ microRNA
━ ━ ━ Mouse
━ ━ ━ ━ in vivo
━ ━ ━ ━ ━ microRNA
━ ━ ━ Rat
━ ━ ━ ━ in vivo
━ ━ ━ ━ ━ microRNA
━ ━ ━ Other
━ ━ ━ ━ in vivo
━ ━ ━ ━ ━ microRNA
━ ━ ━ ━ in vitro
━ ━ ━ ━ ━ Histone modification
━ ━ MOCA
━ ━ ━ Rat
━ ━ ━ ━ in vitro
━ ━ ━ ━ ━ Histone modification
━ ━ Occupational exposure as a painter
━ ━ ━ Human
━ ━ ━ ━ in vivo
━ ━ ━ ━ ━ DNA methylation
━ ━ Sulfur Mustard
━ ━ ━ Human
━ ━ ━ ━ in vitro
━ ━ ━ ━ ━ DNA methylation
━ ━ ━ ━ ━ microRNA
━ ━ ━ ━ in vivo
━ ━ ━ ━ ━ microRNA
━ ━ ━ Mouse
━ ━ ━ ━ in vitro
━ ━ ━ ━ ━ microRNA
━ ━ Vinyl chloride
━ ━ ━ Human
━ ━ ━ ━ in vivo
━ ━ ━ ━ ━ DNA methylation
━ Exclusion
━ ━ no epigenetics
━ ━ ━ y-H2AX
━ ━ ━ histone-carcinogen binding
━ ━ not chemical of interest
━ ━ cannot access full text
━ ━ review or comment
━ ━ other
━ ━ ━ carcinogen binding to (existant) methylated cytosines
━ ━ ━ caricinogen binding and (existant) chromatin structure

References (1685 found)

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