title: Low-dose occupational exposure to benzene and signal transduction pathways involved in the regulation of cellular response to oxidative stress.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Biomedical and Dental Sciences and Morpho-functional Imaging, Occupational Medicine Section, University of Messina, Messina 98125, Italy.
authors.forename: Concettina
authors.initials: C
authors.lastname: Fenga
authors.affiliation: Department of Biomedical and Dental Sciences and Morpho-functional Imaging, Occupational Medicine Section, University of Messina, Messina 98125, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Gangemi
authors.affiliation: Department of Biomedical and Dental Sciences and Morpho-functional Imaging, Occupational Medicine Section, University of Messina, Messina 98125, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Giambò
authors.affiliation: General Chemical State Laboratory of Greece, Department of Hazardous Substances, Mixtures and Articles, 16 An. Tsocha Str, 1152 Athens, Greece.
authors.forename: Christina
authors.initials: C
authors.lastname: Tsitsimpikou
authors.affiliation: Far Eastern Federal University, Vladivostok 690990, Russia.
authors.forename: Kirill
authors.initials: K
authors.lastname: Golokhvast
authors.affiliation: Far Eastern Federal University, Vladivostok 690990, Russia; Laboratory of Toxicology, Medical School, University of Crete, Voutes 71409, Heraklion, Crete, Greece.
authors.forename: Aristidis
authors.initials: A
authors.lastname: Tsatsakis
authors.affiliation: Department of Clinical and Experimental Medicine, University of Messina, University Hospital "G. Martino", Messina 98125, Italy. Electronic address: ccosta@unime.it.
authors.forename: Chiara
authors.initials: C
authors.lastname: Costa
mesh_terms: D000328:Adult; D017209:Apoptosis / Q000187:drug effects; D001554:Benzene / Q000008:administration & dosage / Q000633:toxicity*; D049109:Cell Proliferation / Q000187:drug effects; D005742:Gasoline; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D016273:Occupational Exposure / Q000009:adverse effects*; D018384:Oxidative Stress / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism; D012802:Sicily; D015398:Signal Transduction / Q000187:drug effects*; D013011:Sorbic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D051996:Transcription Factor RelA / Q000378:metabolism
chemical_list: D005742:Gasoline; D017382:Reactive Oxygen Species; D051996:Transcription Factor RelA; C005939:muconic acid; D001554:Benzene; D013011:Sorbic Acid
keywords: Benzene; Cancer; Gasoline station attendants; Peripheral blood mononuclear cells; Signal transduction pathway