Inhalable metal-rich air particles and histone H3K4 dimethylation and H3K9 Acetylation in a Cross-sectional Study of Steel Workers

Laura Cantone, Francesco Nordio, Lifang Hou, Pietro Apostoli, Matteo Bonzini, Letizia Tarantini, Laura Angelici, Valentina Bollati, Antonella Zanobetti, Joel Schwartz, Pier A. Bertazzi, Andrea Baccarelli

Research output: Contribution to journalArticle

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Abstract

Background: Epidemiology investigations have linked exposure to ambient and occupational air particulate matter (PM) with increased risk of lung cancer. PM contains carcinogenic and toxic metals, including arsenic and nickel, which have been shown in in vitro studies to induce histone modifications that activate gene expression by inducing open-chromatin states. Whether inhalation of metal components of PM induces histone modifications in human subjects is undetermined. Objectives: We investigated whether the metal components of PM determined activating histone modifications in 63 steel workers with well-characterized exposure to metal-rich PM. Methods: We determined histone 3 lysine 4 dimethylation (H3K4me2) and histone 3 lysine 9 acetylation (H3K9ac) on histones from blood leukocytes. Exposure to inhalable metal components (aluminum, manganese, nickel, zinc, arsenic, lead, iron) and to total PM was estimated for each study subject. Results: Both H3K4me2 and H3K9ac increased in association with years of employment in the plant (p-trend = 0.04 and 0.006, respectively). H3K4me2 increased in association with air levels of nickel [β = 0.16; 95% confidence interval (CI), 0.03-0.3], arsenic (β = 0.16; 95% CI, 0.02-0.3), and iron (β = 0.14; 95% CI, 0.01-0.26). H3K9ac showed nonsignificant positive associations with air levels of nickel (β = 0.24; 95% CI, -0.02 to 0.51), arsenic (β = 0.21; 95% CI, -0.06 to 0.48), and iron (β = 0.22; 95% CI, -0.03 to 0.47). Cumulative exposures to nickel and arsenic, defined as the product of years of employment by metal air levels, were positively correlated with both H3K4me2 (nickel: β = 0.16; 95% CI, 0.01-0.3; arsenic: β = 0.16; 95% CI, 0.03-0.29) and H3K9ac (nickel: β = 0.27; 95% CI, 0.01-0.54; arsenic: β = 0.28; 95% CI, 0.04-0.51). Conclusions: Our results indicate histone modifications as a novel epigenetic mechanism induced in human subjects by long-term exposure to inhalable nickel and arsenic.

Original languageEnglish
Pages (from-to)964-969
Number of pages6
JournalEnvironmental Health Perspectives
Volume119
Issue number7
DOIs
Publication statusPublished - Jul 2011

Fingerprint

Steel
Acetylation
Histones
Arsenic
Nickel
Cross-Sectional Studies
Metals
Air
Particulate Matter
Confidence Intervals
Histone Code
Iron
Lysine
Poisons
Manganese
Aluminum
Epigenomics
Inhalation
Chromatin
Zinc

Keywords

  • Environmental carcinogens
  • Epigenetics
  • Histone modifications
  • Metals
  • Particulate matter

ASJC Scopus subject areas

  • Health, Toxicology and Mutagenesis
  • Public Health, Environmental and Occupational Health

Cite this

Inhalable metal-rich air particles and histone H3K4 dimethylation and H3K9 Acetylation in a Cross-sectional Study of Steel Workers. / Cantone, Laura; Nordio, Francesco; Hou, Lifang; Apostoli, Pietro; Bonzini, Matteo; Tarantini, Letizia; Angelici, Laura; Bollati, Valentina; Zanobetti, Antonella; Schwartz, Joel; Bertazzi, Pier A.; Baccarelli, Andrea.

In: Environmental Health Perspectives, Vol. 119, No. 7, 07.2011, p. 964-969.

Research output: Contribution to journalArticle

Cantone, L, Nordio, F, Hou, L, Apostoli, P, Bonzini, M, Tarantini, L, Angelici, L, Bollati, V, Zanobetti, A, Schwartz, J, Bertazzi, PA & Baccarelli, A 2011, 'Inhalable metal-rich air particles and histone H3K4 dimethylation and H3K9 Acetylation in a Cross-sectional Study of Steel Workers', Environmental Health Perspectives, vol. 119, no. 7, pp. 964-969. https://doi.org/10.1289/ehp.1002955
Cantone, Laura ; Nordio, Francesco ; Hou, Lifang ; Apostoli, Pietro ; Bonzini, Matteo ; Tarantini, Letizia ; Angelici, Laura ; Bollati, Valentina ; Zanobetti, Antonella ; Schwartz, Joel ; Bertazzi, Pier A. ; Baccarelli, Andrea. / Inhalable metal-rich air particles and histone H3K4 dimethylation and H3K9 Acetylation in a Cross-sectional Study of Steel Workers. In: Environmental Health Perspectives. 2011 ; Vol. 119, No. 7. pp. 964-969.
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abstract = "Background: Epidemiology investigations have linked exposure to ambient and occupational air particulate matter (PM) with increased risk of lung cancer. PM contains carcinogenic and toxic metals, including arsenic and nickel, which have been shown in in vitro studies to induce histone modifications that activate gene expression by inducing open-chromatin states. Whether inhalation of metal components of PM induces histone modifications in human subjects is undetermined. Objectives: We investigated whether the metal components of PM determined activating histone modifications in 63 steel workers with well-characterized exposure to metal-rich PM. Methods: We determined histone 3 lysine 4 dimethylation (H3K4me2) and histone 3 lysine 9 acetylation (H3K9ac) on histones from blood leukocytes. Exposure to inhalable metal components (aluminum, manganese, nickel, zinc, arsenic, lead, iron) and to total PM was estimated for each study subject. Results: Both H3K4me2 and H3K9ac increased in association with years of employment in the plant (p-trend = 0.04 and 0.006, respectively). H3K4me2 increased in association with air levels of nickel [β = 0.16; 95{\%} confidence interval (CI), 0.03-0.3], arsenic (β = 0.16; 95{\%} CI, 0.02-0.3), and iron (β = 0.14; 95{\%} CI, 0.01-0.26). H3K9ac showed nonsignificant positive associations with air levels of nickel (β = 0.24; 95{\%} CI, -0.02 to 0.51), arsenic (β = 0.21; 95{\%} CI, -0.06 to 0.48), and iron (β = 0.22; 95{\%} CI, -0.03 to 0.47). Cumulative exposures to nickel and arsenic, defined as the product of years of employment by metal air levels, were positively correlated with both H3K4me2 (nickel: β = 0.16; 95{\%} CI, 0.01-0.3; arsenic: β = 0.16; 95{\%} CI, 0.03-0.29) and H3K9ac (nickel: β = 0.27; 95{\%} CI, 0.01-0.54; arsenic: β = 0.28; 95{\%} CI, 0.04-0.51). Conclusions: Our results indicate histone modifications as a novel epigenetic mechanism induced in human subjects by long-term exposure to inhalable nickel and arsenic.",
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author = "Laura Cantone and Francesco Nordio and Lifang Hou and Pietro Apostoli and Matteo Bonzini and Letizia Tarantini and Laura Angelici and Valentina Bollati and Antonella Zanobetti and Joel Schwartz and Bertazzi, {Pier A.} and Andrea Baccarelli",
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T1 - Inhalable metal-rich air particles and histone H3K4 dimethylation and H3K9 Acetylation in a Cross-sectional Study of Steel Workers

AU - Cantone, Laura

AU - Nordio, Francesco

AU - Hou, Lifang

AU - Apostoli, Pietro

AU - Bonzini, Matteo

AU - Tarantini, Letizia

AU - Angelici, Laura

AU - Bollati, Valentina

AU - Zanobetti, Antonella

AU - Schwartz, Joel

AU - Bertazzi, Pier A.

AU - Baccarelli, Andrea

PY - 2011/7

Y1 - 2011/7

N2 - Background: Epidemiology investigations have linked exposure to ambient and occupational air particulate matter (PM) with increased risk of lung cancer. PM contains carcinogenic and toxic metals, including arsenic and nickel, which have been shown in in vitro studies to induce histone modifications that activate gene expression by inducing open-chromatin states. Whether inhalation of metal components of PM induces histone modifications in human subjects is undetermined. Objectives: We investigated whether the metal components of PM determined activating histone modifications in 63 steel workers with well-characterized exposure to metal-rich PM. Methods: We determined histone 3 lysine 4 dimethylation (H3K4me2) and histone 3 lysine 9 acetylation (H3K9ac) on histones from blood leukocytes. Exposure to inhalable metal components (aluminum, manganese, nickel, zinc, arsenic, lead, iron) and to total PM was estimated for each study subject. Results: Both H3K4me2 and H3K9ac increased in association with years of employment in the plant (p-trend = 0.04 and 0.006, respectively). H3K4me2 increased in association with air levels of nickel [β = 0.16; 95% confidence interval (CI), 0.03-0.3], arsenic (β = 0.16; 95% CI, 0.02-0.3), and iron (β = 0.14; 95% CI, 0.01-0.26). H3K9ac showed nonsignificant positive associations with air levels of nickel (β = 0.24; 95% CI, -0.02 to 0.51), arsenic (β = 0.21; 95% CI, -0.06 to 0.48), and iron (β = 0.22; 95% CI, -0.03 to 0.47). Cumulative exposures to nickel and arsenic, defined as the product of years of employment by metal air levels, were positively correlated with both H3K4me2 (nickel: β = 0.16; 95% CI, 0.01-0.3; arsenic: β = 0.16; 95% CI, 0.03-0.29) and H3K9ac (nickel: β = 0.27; 95% CI, 0.01-0.54; arsenic: β = 0.28; 95% CI, 0.04-0.51). Conclusions: Our results indicate histone modifications as a novel epigenetic mechanism induced in human subjects by long-term exposure to inhalable nickel and arsenic.

AB - Background: Epidemiology investigations have linked exposure to ambient and occupational air particulate matter (PM) with increased risk of lung cancer. PM contains carcinogenic and toxic metals, including arsenic and nickel, which have been shown in in vitro studies to induce histone modifications that activate gene expression by inducing open-chromatin states. Whether inhalation of metal components of PM induces histone modifications in human subjects is undetermined. Objectives: We investigated whether the metal components of PM determined activating histone modifications in 63 steel workers with well-characterized exposure to metal-rich PM. Methods: We determined histone 3 lysine 4 dimethylation (H3K4me2) and histone 3 lysine 9 acetylation (H3K9ac) on histones from blood leukocytes. Exposure to inhalable metal components (aluminum, manganese, nickel, zinc, arsenic, lead, iron) and to total PM was estimated for each study subject. Results: Both H3K4me2 and H3K9ac increased in association with years of employment in the plant (p-trend = 0.04 and 0.006, respectively). H3K4me2 increased in association with air levels of nickel [β = 0.16; 95% confidence interval (CI), 0.03-0.3], arsenic (β = 0.16; 95% CI, 0.02-0.3), and iron (β = 0.14; 95% CI, 0.01-0.26). H3K9ac showed nonsignificant positive associations with air levels of nickel (β = 0.24; 95% CI, -0.02 to 0.51), arsenic (β = 0.21; 95% CI, -0.06 to 0.48), and iron (β = 0.22; 95% CI, -0.03 to 0.47). Cumulative exposures to nickel and arsenic, defined as the product of years of employment by metal air levels, were positively correlated with both H3K4me2 (nickel: β = 0.16; 95% CI, 0.01-0.3; arsenic: β = 0.16; 95% CI, 0.03-0.29) and H3K9ac (nickel: β = 0.27; 95% CI, 0.01-0.54; arsenic: β = 0.28; 95% CI, 0.04-0.51). Conclusions: Our results indicate histone modifications as a novel epigenetic mechanism induced in human subjects by long-term exposure to inhalable nickel and arsenic.

KW - Environmental carcinogens

KW - Epigenetics

KW - Histone modifications

KW - Metals

KW - Particulate matter

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