Benzene Exposure Linked to Aberrant Gene Expression and Hematotoxicity

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Researchers in Wuhan, People's Republic of China, have found that benzene exposure causes aberrant gene expression and is linked to hematotoxicity and leukemia in humans. The study analyzed gene expression in peripheral mononuclear blood cells from seven workers diagnosed with benzene poisoning and seven matched controls. The results showed that 22 genes were up-regulated and 18 down-regulated in benzene patients compared with controls.

Key Takeaways:

  • Two benzene-regulated genes, CYP4F3A and DNA-dependent protein kinase catalytic subunit (DNA-PKcs), were identified and characterized.
  • CYP4F3A, which encodes the leukotriene B(4) (LTB(4)) omega-hydroxylase, was found to be elevated in all patients and induced by benzene metabolite phenol in HL-60 and K562 cells as well as ex vivo in human peripheral neutrophils.
  • Silencing of CYP4F3A in HL-60 cells reduced cell survival to 3% at 7 days, indicating that CYP4F3A is a critical positive regulator of HL-60 proliferation.
  • Hydroquinone induced the formation of gamma-H2AX foci, a marker of DNA double strand breaks (DSBs), in HL-60 cells, and DNA-PKcs mRNA and protein were induced by hydroquinone in HL-60 cells.
  • Induction of DNA-PKcs and non-homologous end joining (NHEJ) may contribute to mutagenesis and leukemia by benzene.

Statistics:

  • 22 genes were up-regulated and 18 down-regulated in benzene patients compared with controls.
  • CYP4F3A mRNA was elevated in all patients.
  • DNA-PKcs mRNA and protein were induced by hydroquinone in HL-60 cells.
  • Silencing of CYP4F3A in HL-60 cells reduced cell survival to 56%, 44%, 22%, 14%, and 3% at 3, 4, 5, 6, and 7 days, respectively.

Sources:

  • Y. Bi et al., "Gene expression in benzene-exposed workers by microarray analysis of peripheral mononuclear blood cells: induction and silencing of CYP4F3A and regulation of DNA-dependent protein kinase catalytic subunit in DNA double strand break repair." Chemico-biological Interactions, 2010;184(1-2):207-11.