Effects of particulate matter on genomic DNA methylation content and iNOS promoter methylation.
BACKGROUND
Altered patterns of gene expression mediate the effects of particulate matter (PM) on human health, but mechanisms through which PM modifies gene expression are largely undetermined.


OBJECTIVE
We aimed at identifying short- and long-term effects of PM exposure on DNA methylation, a major genomic mechanism of gene expression control, in workers in an electric furnace steel plant with well-characterized exposure to PM with aerodynamic diameters < 10 microm (PM(10)).


METHODS
We measured global genomic DNA methylation content estimated in Alu and long interspersed nuclear element-1 (LINE-1) repeated elements, and promoter DNA methylation of iNOS (inducible nitric oxide synthase), a gene suppressed by DNA methylation and induced by PM exposure in blood leukocytes. Quantitative DNA methylation analysis was performed through bisulfite PCR pyrosequencing on blood DNA obtained from 63 workers on the first day of a work week (baseline, after 2 days off work) and after 3 days of work (postexposure). Individual PM(10) exposure was between 73.4 and 1,220 microg/m(3).


RESULTS
Global methylation content estimated in Alu and LINE-1 repeated elements did not show changes in postexposure measures compared with baseline. PM(10) exposure levels were negatively associated with methylation in both Alu [beta = -0.19 %5-methylcytosine (%5mC); p = 0.04] and LINE-1 [beta = -0.34 %5mC; p = 0.04], likely reflecting long-term PM(10) effects. iNOS promoter DNA methylation was significantly lower in postexposure blood samples compared with baseline (difference = -0.61 %5mC; p = 0.02).


CONCLUSIONS
We observed changes in global and gene specific methylation that should be further characterized in future investigations on the effects of PM.
Tarantini
Letizia
L
Laboratory of Environmental Epigenetics, Department of Preventive Medicine, University of Milan and IRCCS Maggiore Hospital, Milan, Italy.
Bonzini
Matteo
M
Apostoli
Pietro
P
Pegoraro
Valeria
V
Bollati
Valentina
V
Marinelli
Barbara
B
Cantone
Laura
L
Rizzo
Giovanna
G
Hou
Lifang
L
Schwartz
Joel
J
Bertazzi
Pier Alberto
PA
Baccarelli
Andrea
A
D000328:Adult; D019175:DNA Methylation / Q000187:drug effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D052247:Nitric Oxide Synthase Type II / Q000235:genetics*; D052638:Particulate Matter / Q000633:toxicity*; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic / Q000235:genetics*
D052638:Particulate Matter; D052247:Nitric Oxide Synthase Type II