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

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• 作者：Concettina Fenga^a ; Silvia Gangemi^a ; Federica Giambò ; ^a ; Christina Tsitsimpikou^b ; Kirill Golokhvast^c ; Aristidis Tsatsakis^c ; ^d ; Chiara Costa^e ; ^{ccosta@unime.it" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Benzene ; Cancer ; Signal transduction pathway ; Peripheral blood mononuclear cells ; Gasoline station attendants
• 刊名：Life Sciences
• 出版年：2016
• 出版时间：15 February 2016
• 年：2016
• 卷：147
• 期：Complete
• 页码：67-70
• 全文大小：288 K

文摘

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.