Background Inhaled particles have been shown to produce systemic changes in DNA methylation. Global hypomethylation has been associated to viral sequence reactivation, possibly linked to the activation of pro-inflammatory pathways occurring after exposure. This observation provides a rationale to investigate viral sequence (both exogenous and endogenous) methylation in association to metal-rich particulate matter exposure. To verify this hypothesis, we chose the Wp promoter of the Epstein-Barr Virus (EBV-Wp) and the promoter of the human-endogenous-retrovirus w (HERV-w), respectively as a paradigm of an exogenous and an endogenous retroviral sequence, to be investigated by bisulfite PCR Pyrosequencing. We enrolled 63 male workers in an electric furnace steel plant, exposed to high level of metal-rich particulate matter. Results Comparing samples obtained in the first day of a work week (time 0-baseline, after 2 days off work) and the samples obtained after 3 days of work (time 1-post exposure), the mean methylation of EBV-Wp was significantly higher at baseline compared to post-exposure (meanbaseline= 56.7%5mC; meanpost-exposure= 47.9%5mC; p-value = 0.009), whereas the mean methylation of HERV-w did not significantly differ. Individual exposure to inhalable particles and metals was estimated based on measures in all working areas and time spent by the study subjects in each area. In a regression model adjusted for age, body mass index and smoking, PM and metal components had a positive association with EBV-Wp methylation (i.e. PM10: β = 5.99, p-value < 0.038; nickel: β = 17.82, p-value = 0.02; arsenic: β = 13.59, p-value < 0.015). Conclusions The difference observed comparing baseline and post-exposure samples may be suggestive of a rapid change in EBV methylation induced by air particles, while correlation between EBV methylation and PM/metal exposure may represent a more stable adaptive mechanism. Future studies investigating a larger panel of viral sequences could better elucidate possible mechanisms and their role in pro-inflammatory pathways leading to systemic health effects.

Effects of metal-rich particulate matter exposure on exogenous and endogenous viral sequence methylation in healthy steel-workers / R. Mercorio, M. Bonzini, L. Angelici, S. Iodice, S. Delbue, J. Mariani, P. Apostoli, A.C. Pesatori, V. Bollati. - In: ENVIRONMENTAL RESEARCH. - ISSN 0013-9351. - 159(2017 Nov), pp. 452-457. [10.1016/j.envres.2017.08.042]

Effects of metal-rich particulate matter exposure on exogenous and endogenous viral sequence methylation in healthy steel-workers

R. Mercorio
Primo
;
M. Bonzini
Secondo
;
L. Angelici;S. Iodice;S. Delbue;J. Mariani;A.C. Pesatori
Penultimo
;
V. Bollati
Ultimo
2017

Abstract

Background Inhaled particles have been shown to produce systemic changes in DNA methylation. Global hypomethylation has been associated to viral sequence reactivation, possibly linked to the activation of pro-inflammatory pathways occurring after exposure. This observation provides a rationale to investigate viral sequence (both exogenous and endogenous) methylation in association to metal-rich particulate matter exposure. To verify this hypothesis, we chose the Wp promoter of the Epstein-Barr Virus (EBV-Wp) and the promoter of the human-endogenous-retrovirus w (HERV-w), respectively as a paradigm of an exogenous and an endogenous retroviral sequence, to be investigated by bisulfite PCR Pyrosequencing. We enrolled 63 male workers in an electric furnace steel plant, exposed to high level of metal-rich particulate matter. Results Comparing samples obtained in the first day of a work week (time 0-baseline, after 2 days off work) and the samples obtained after 3 days of work (time 1-post exposure), the mean methylation of EBV-Wp was significantly higher at baseline compared to post-exposure (meanbaseline= 56.7%5mC; meanpost-exposure= 47.9%5mC; p-value = 0.009), whereas the mean methylation of HERV-w did not significantly differ. Individual exposure to inhalable particles and metals was estimated based on measures in all working areas and time spent by the study subjects in each area. In a regression model adjusted for age, body mass index and smoking, PM and metal components had a positive association with EBV-Wp methylation (i.e. PM10: β = 5.99, p-value < 0.038; nickel: β = 17.82, p-value = 0.02; arsenic: β = 13.59, p-value < 0.015). Conclusions The difference observed comparing baseline and post-exposure samples may be suggestive of a rapid change in EBV methylation induced by air particles, while correlation between EBV methylation and PM/metal exposure may represent a more stable adaptive mechanism. Future studies investigating a larger panel of viral sequences could better elucidate possible mechanisms and their role in pro-inflammatory pathways leading to systemic health effects.
DNA methylation; Epstein-Barr virus; heavy metals; human endogenous retrovirus w; PM exposure; adult; air pollutants; DNA Methylation; DNA, viral; endogenous retroviruses; herpesvirus 4, human; humans; Italy; male; metals; middle aged; particulate matter; polymerase chain reaction; promoter regions, genetic; steel; metallurgy; occupational exposure; biochemistry; 2300
Settore MED/44 - Medicina del Lavoro
   Susceptibily to Particle Healt Effects, miRNAs and Exosomes
   SPHERE
   EUROPEAN COMMISSION
   FP7
   282413
nov-2017
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/551090
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