Global Levels of Histone Modifications in Peripheral Blood Mononuclear Cells of Subjects with Exposure to Nickel

• Published in: Environmental health perspectives Vol. 120; no. 2; pp. 198 - 203
• Main Authors: Arita, Adriana, Niu, Jingping, Qu, Qingshan, Zhao, Najuan, Ruan, Ye, Nadas, Arthur, Chervona, Yana, Wu, Fen, Sun, Hong, Hayes, Richard B., Costa, Max
• Format: Journal Article
• Language: English
• Published: Research Triangle Park, NC National Institute of Environmental Health Sciences 01.02.2012; US Department of Health and Human Services
• Subjects: Acetylation; Acetylation - drug effects; Adult; Biological and medical sciences; Blood cells; Chemical and industrial products toxicology. Toxic occupational diseases; Chemical hazards; China; Cigarette smoking; Cotinine - urine; Creatinine - urine; DNA Methylation - drug effects; Dust - analysis; Environment. Living conditions; Environmental aspects; Environmental health; Enzyme-Linked Immunosorbent Assay; Epigenetics; Exposure; Genetic aspects; Health aspects; Histone Code; Histones; Histones - metabolism; Humans; Leukocytes, Mononuclear - chemistry; Male; Mass Spectrometry; Medical sciences; Metallurgy; Metals and various inorganic compounds; Methylation; Middle Aged; Nickel; Nickel - toxicity; Nickel - urine; Occupational Exposure; Physiological aspects; Public health. Hygiene; Public health. Hygiene-occupational medicine; Referents; Regression Analysis; Smoking - adverse effects; Toxicology; Urine; Young Adult; China; United States; Human; Modification; interindividual variation; intraindividual variation; Transition metal; Refinery; histone modifications; Occupational exposure; H3K9 dimethylation; Blood cell; H3K9 acetylation; Mononuclear cell; Health and environment; Intraindividual comparison; H3K4 trimethylation; Interindividual comparison; Epigenetics; Worker; Nickel; Acetylation; Histone; Occupational medicine; nickel refinery workers
• ISSN: 0091-6765; 1552-9924; 1552-9924
• DOI: 10.1289/ehp.1104140

Background: Occupational exposure to nickel (Ni) is associated with an increased risk for lung and nasal cancers. Ni compounds exhibit weak mutagenic activity, cause gene amplification, and disrupt cellular epigenetic homeostasis. However, the Ni-induced changes in global histone modification levels have only been tested in vitro. Objective: This study was conducted in a Chinese population to determine whether occupational exposure to Ni is associated with alterations of global histone modification levels and to evaluate the inter-and intraindividual variance of global histone modification levels. Method: Forty-five subjects with occupational exposure to Ni and 75 referents were recruited. Urinary Ni and global H3K4 trimethylation, H3K9 acetylation, and H3K9 dimethylation levels were measured in peripheral blood mononuclear cells (PBMCs) of subjects. Results: H3K4me3 was elevated in Ni-exposed subjects (0.25% ± 0.11%) compared with referents (0.15% ± 0.04%; P = 0.0004), and H3K9me2 was decreased (Ni-exposed subjects, 0.11% ± 0.05%; referents, 0.15% ± 0.04%; P= 0.003). H3K4me3 was positively (r = 0.4, p = 0.0008) and H3K9ac was negatively (r = 0.1, P =0.01) associated with urinary Ni. Interindividual variances of H3K4me3, H3K9ac, and H3K9me2 were larger compared with intraindividual variance in both exposure test groups, resulting in reliability coefficients (an estimate of consistency of a set of measurements) of 0.60, 0.67, and 0.79 for H3K4me3, H3K9ac, and H3K9me2, respectively, for Ni-exposed subjects and of 0.75, 0.74, and 0.97, respectively, for referent subjects. Conclusion: The results of this study indicate that occupational exposure to Ni is associated with alterations of global histone modification levels and that measurements of global levels of histone modifications are relatively stable over time in human PBMCs.