Low-dose occupational exposure to benzene and signal transduction pathways involved in the regulation of cellular response to oxidative stress

Life Sci. 2016 Feb 15:147:67-70. doi: 10.1016/j.lfs.2015.12.025. Epub 2016 Jan 14.

Abstract

Aims: Benzene metabolism seems to modulate NF-κB, p38-MAPK (mitogen-activated protein kinase) and signal transducer and activator of transcription 3 (STAT3) signalling pathways via the production of reactive oxygen species. This study aims to evaluate the effects of low-dose, long-term exposure on NF-κB, STAT3, p38-MAPK and stress-activated protein kinase/Jun amino-terminal kinase (SAPK/JNK) signal transduction pathways in peripheral blood mononuclear cells in gasoline station attendants. The influence of consumption of vegetables and fruits on these pathways has also been evaluated.

Main methods: A total of 91 men, employed in gasoline stations located in eastern Sicily, were enrolled for this study and compared with a control group of 63 male office workers with no history of exposure to benzene. The exposure was assessed by measuring urinary trans,trans-muconic acid (t,t-MA) concentration. Quantitative analyses were performed for proteins NF-κB p65, phospho-NF-κB p65, phospho-IκB-α, phospho-SAPK/JNK, phospho-p38 MAPK and phospho-STAT3 using an immunoenzymatic assay.

Key findings: The results of this study indicate significantly higher t,t-MA levels in gasoline station attendants. With regard to NF-κB, phospho-IκB-α and phospho-STAT3 proteins, statistically significant differences were observed in workers exposed to benzene. However, no differences were observed in SAPK/JNK and p38-MAPK activation. These changes were positively correlated with t,t-MA levels, but only phospho-NF-κB p65 was associated with the intake of food rich in antioxidant active principles.

Significance: Chronic exposure to low-dose benzene can modulate signal transduction pathways activated by oxidative stress and involved in cell proliferation and apoptosis. This could represent a possible mechanism of carcinogenic action of chronic benzene exposure.

Keywords: Benzene; Cancer; Gasoline station attendants; Peripheral blood mononuclear cells; Signal transduction pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Apoptosis / drug effects
  • Benzene / administration & dosage
  • Benzene / toxicity*
  • Cell Proliferation / drug effects
  • Gasoline
  • Humans
  • Leukocytes, Mononuclear / metabolism
  • Male
  • Middle Aged
  • Occupational Exposure / adverse effects*
  • Oxidative Stress / drug effects*
  • Reactive Oxygen Species / metabolism
  • Sicily
  • Signal Transduction / drug effects*
  • Sorbic Acid / analogs & derivatives
  • Sorbic Acid / metabolism
  • Transcription Factor RelA / metabolism

Substances

  • Gasoline
  • Reactive Oxygen Species
  • Transcription Factor RelA
  • muconic acid
  • Benzene
  • Sorbic Acid