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Effects of Exposure to Metal Rich Air Particles on Histone H3-K4 Dimethylation and H3-K9 Acetylation

Cantone, Laura*; Pegoraro, Valeria*; Apostoli, Pietro; Bonzini, Matteo§; Pesatori, Angela Cecilia*; Tarantini, Letizia*; Bollati, Valentina*; Schwartz, Joel; Bertazzi, Pietro Alberto*; Baccarelli, Andrea*

doi: 10.1097/01.ede.0000362279.31562.68
Abstracts: ISEE 21st Annual Conference, Dublin, Ireland, August 25–29, 2009: Oral Presentations

*University of Milan and IRCCS Maggiore Hospital, Milan, Italy; †University of Brescia, Brescia, Italy; ‡Harvard School of Public Health, Boston, United States; and §University of Insubria, Varese, Italy.

Abstracts published in Epidemiology have been reviewed by the organizations of Epidemiology. Affliate Societies at whose meetings the abstracts have been accepted for presentation. These abstracts have not undergone review by the Editorial Board of Epidemiology.


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Background and Objectives:

Alteration in epigenetic regulation of gene expression is a frequent event in human cancer. The detrimental effects of inhalation of ambient and occupational air particles on respiratory and cardiovascular disease have been linked to systemic deregulation of gene expression. In vitro studies have shown that metal components of air particles, such as Cr and Ni, may determine histone acetylation or methylation, a main epigenetic mechanism for chromatin remodelling, and chronic exposure to these metal compounds could increase cancer incidence. Whether inhalation of metal particle components could modify histone modifications in humans is unresolved. We investigated whether metal components of air particles determine histone modifications in workers in an electric-furnace steel plant with well-characterized exposure to air particles and related metal components.

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We extracted total histones from blood collected from 63 workers on the last day of a workweek following three consecutive work days. Individual exposure to particulate matter with aerodynamic diameter <10μm (PM10) or <1μm (PM1), and metals (Cr, Pb, Cd, As, Ni, Mn) was estimated using work area measurements and time-activity records. We determined histone H3-K4 dimethylation and H3-K9 acetylation using PathScan Sandwich ELISA kits (Cell Signaling Technology).

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H3-K4 dimethylation and H3-K9 acetylation were not associated with levels of PM mass (H3K4m2: β = 0.03, P = 0.34 for PM10, β = 0.02, P = 0.56 for PM1; H3K9ac: β = −0.07, P = 0.23 for PM10, β = −0.03, P = 0.70 for PM1). H3-K4 dimethylation increased in association with air levels of Cr (β = 0.18; P = 0.005), Pb (β = 0.18; P = 0.01), As (β = 0.16; P = 0.03) and Ni (β = 0.15; P = 0.04). H3-K9 acetylation showed a borderline negative association with airborne cadmium (β = −0.26; P = 0.06).

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Our results indicate histone modifications as a novel epigenetic mechanism induced by metal components of air particles in human subjects.

© 2009 Lippincott Williams & Wilkins, Inc.