Nickel and histone modifications in vivo.
Occupational exposure to nickel (Ni) is associated with an
increased risk of lung and nasal cancers. Ni compounds exhibit weak
mutagenie activity, cause gene amplification, and disrupt cellular
epigenetic homeostasis. However, Ni-induced changes in global histone modification levels have only been tested in vitro, Arita et al. (p.
198) conducted a study 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.
Forty-five subjects with occupational exposure to Ni and 75 referents
were recruited. Levels of urinary Ni and global H3K4 trimethylation
(H3K4me3), H3K9 acetylation (H3K9ac), and H3K9 dimethylation (H3K9me2)
were measured in peripheral blood mononuclear cells (PBMCs). H3K4me3
levels were elevated and H3K9me2 levels were decreased in Ni-exposed
subjects. H3K4me3 was positively associated and H3K9ac was negatively
associated with urinary Ni. Interindividual variances of H3K4me3,
H3K9ac, and H3K9me2 were larger relative to intraindividual variance in
both groups, which resulted in reliability coefficients of 0.75, 0.74,
and 0.97 for H3K4me3, H3K9ac, and H3K9me2, respectively, for referent
subjects. For the Ni-exposed subjects, the authors report reliability
coefficients of 0.60, 0.67, and 0.79 for H3K4me3, H3K9ac, and H3K9me2,
respectively. i1hey conclude 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 rime in human PBMCs.