Global levels of histone modifications in peripheral blood mononuclear cells of subjects with exposure to nickel.
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.


METHODS
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.


CONCLUSIONS
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.
Department of Environmental Medicine, New York University School of Medicine, New York, New York, USA.
Adriana
A
Arita
Jingping
J
Niu
Qingshan
Q
Qu
Najuan
N
Zhao
Ye
Y
Ruan
Arthur
A
Nadas
Yana
Y
Chervona
Fen
F
Wu
Hong
H
Sun
Richard B
RB
Hayes
Max
M
Costa
D000107:Acetylation / Q000187:drug effects; D000328:Adult; D002681:China; D003367:Cotinine / Q000652:urine; D003404:Creatinine / Q000652:urine; D019175:DNA Methylation / Q000187:drug effects; D004391:Dust / Q000032:analysis; D004797:Enzyme-Linked Immunosorbent Assay; D042421:Histone Code; D006657:Histones / Q000378:metabolism; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000737:chemistry*; D008297:Male; D013058:Mass Spectrometry; D008669:Metallurgy; D008875:Middle Aged; D009532:Nickel / Q000633:toxicity* / Q000652:urine; D016273:Occupational Exposure; D012044:Regression Analysis; D012907:Smoking / Q000009:adverse effects; D055815:Young Adult
D004391:Dust; D006657:Histones; D009532:Nickel; D003404:Creatinine; D003367:Cotinine