DNA methylation differences in exposed workers and nearby residents of the Ma Ta Phut industrial estate, Rayong, Thailand.
BACKGROUND
Adverse biological effects from airborne pollutants are a primary environmental concern in highly industrialized areas. Recent studies linked air pollution exposures with altered blood Deoxyribo-nucleic acid (DNA) methylation, but effects from industrial sources and underlying biological mechanisms are still largely unexplored.


METHODS
The Ma Ta Phut industrial estate (MIE) in Rayong, Thailand hosts one of the largest steel, oil refinery and petrochemical complexes in south-eastern Asia. We measured a panel of blood DNA methylation markers previously associated with air pollution exposures, including repeated elements [long interspersed nuclear element-1 (LINE-1) and Alu] and genes [p53, hypermethylated-in-cancer-1 (HIC1), p16 and interleukin-6 (IL-6)], in 67 MIE workers, 65 Ma Ta Phut residents and 45 rural controls. To evaluate the role of DNA damage and oxidation, we correlated DNA methylation measures with bulky DNA and 3-(2-deoxy-β-D-erythro-pentafuranosyl)pyrimido[1,2-α]purin-10(3H)-one deoxyguanosine (M(1)dG) adducts.


RESULTS
In covariate-adjusted models, MIE workers, compared with rural residents, showed lower LINE-1 (74.8% vs 78.0%; P < 0.001), p53 (8.0% vs 15.7%; P < 0.001) and IL-6 methylation (39.2% vs 45.0%; P = 0.027) and higher HIC1 methylation (22.2% vs 15.3%, P < 0.001). For all four markers, Ma Ta Phut residents exhibited methylation levels intermediate between MIE workers and rural controls (LINE-1, 75.7%, P < 0.001; p53, 9.0%, P < 0.001; IL-6, 39.8%, P = 0.041; HIC1, 17.8%, P = 0.05; all P-values vs rural controls). Bulky DNA adducts showed negative correlation with p53 methylation (P = 0.01). M(1)dG showed negative correlations with LINE-1 (P = 0.003) and IL-6 methylation (P = 0.05).


CONCLUSIONS
Our findings indicate that industrial exposures may induce alterations of DNA methylation patterns detectable in blood leucocyte DNA. Correlation of DNA adducts with DNA hypomethylation suggests potential mediation by DNA damage.
Cancer Risk Factor Branch, Cancer Prevention and Research Institute, Florence, Italy.
Marco
M
Peluso
Valentina
V
Bollati
Armelle
A
Munnia
Petcharin
P
Srivatanakul
Adisorn
A
Jedpiyawongse
Suleeporn
S
Sangrajrang
Sara
S
Piro
Marcello
M
Ceppi
Pier Alberto
PA
Bertazzi
Paolo
P
Boffetta
Andrea A
AA
Baccarelli
D000328:Adult; D000395:Air Pollutants, Occupational / Q000633:toxicity*; D000397:Air Pollution / Q000009:adverse effects*; D015415:Biomarkers; D019175:DNA Methylation / Q000187:drug effects*; D004032:Diet; D004781:Environmental Exposure / Q000009:adverse effects* / Q000706:statistics & numerical data; D019652:Extraction and Processing Industry; D005260:Female; D006801:Humans; D007962:Leukocytes; D008297:Male; D016273:Occupational Exposure / Q000009:adverse effects / Q000706:statistics & numerical data; D009790:Occupations / Q000706:statistics & numerical data; D012424:Rural Population / Q000706:statistics & numerical data; D012907:Smoking / Q000453:epidemiology; D013785:Thailand / Q000453:epidemiology; D014505:Urban Population / Q000706:statistics & numerical data
D000395:Air Pollutants, Occupational; D015415:Biomarkers