title: Increased methylation of repetitive elements and DNA repair genes is associated with higher DNA oxidation in children in an urbanized, industrial environment.
abstract: DNA methylation in DNA repair genes participates in the DNA damage regulation. Particulate matter (PM), which has metals and polycyclic aromatic hydrocarbons (PAHs) adsorbed, among others has been linked to adverse health outcomes and may modify DNA methylation. To evaluate PM exposure impact on repetitive elements and gene-specific DNA methylation and DNA damage, we conducted a cross-sectional study in 150 schoolchildren (7-10 years old) from an urbanized, industrial area of the metropolitan area of Mexico City (MAMC), which frequently exhibits PM concentrations above safety standards. Methylation (5mC) of long interspersed nuclear element-1 (LINE1) and DNA repair gene (OGG1, APEX, and PARP1) was assessed by pyrosequencing in peripheral mononuclear cells, DNA damage by comet assay and DNA oxidation by 8-OHdG content. PAH and metal contents in PM10(≤10μm aerodynamic diameter) were determined by HPLC-MS and ICP-AES, respectively. Multiple regression analysis between DNA methylation, DNA damage, and PM10exposure showed that PM10was significantly associated with oxidative DNA damage; a 1% increase in 5mC at all CpG sites in PARP1 promoter was associated with a 35% increase in 8-OHdG, while a 1% increase at 1, 2, and 3 CpG sites resulted in 38, 9, and 56% increments, respectively. An increase of 10pg/m3in benzo[b]fluoranthene content of PM10was associated with a 6% increase in LINE1 methylation. Acenaphthene, indene [1,2,3-cd] pyrene, and pyrene concentrations correlated with higher dinucleotide methylation in OGG1, APEX and PARP1 genes, respectively. Vanadium concentration correlated with increased methylation at selected APEX and PARP1 CpG sites. DNA repair gene methylation was significantly correlated with DNA damage and with specific PM10-associated PAHs and Vanadium. Data suggest that exposure to PM and its components are associated with differences in DNA methylation of repair genes in children, which may contribute to DNA damage.
authors.affiliation: Toxicology Department, CINVESTAV-IPN, Mexico City, Mexico. Electronic address: mialvarado@cinvestav.mx.
authors.forename: Isabel
authors.initials: I
authors.lastname: Alvarado-Cruz
authors.affiliation: Toxicology Department, CINVESTAV-IPN, Mexico City, Mexico. Electronic address: msanchez@hsph.harvard.edu.
authors.forename: Marco
authors.initials: M
authors.lastname: Sánchez-Guerra
authors.affiliation: National Institute of Public Health, Mexico City, Mexico. Electronic address: lhcadena@insp.mx.
authors.forename: Leticia
authors.initials: L
authors.lastname: Hernández-Cadena
authors.affiliation: Toxicology Department, CINVESTAV-IPN, Mexico City, Mexico. Electronic address: avizcaya@cinvestav.mx.
authors.forename: Andrea
authors.initials: A
authors.lastname: De Vizcaya-Ruiz
authors.affiliation: Autonomous Metropolitan University, Mexico City, Mexico. Electronic address: vma@correo.azc.uam.mx.
authors.forename: Violeta
authors.initials: V
authors.lastname: Mugica
authors.affiliation: Toxicology Department, CINVESTAV-IPN, Mexico City, Mexico. Electronic address: na_pelallom@yahoo.com.mx.
authors.forename: Nadia Azenet
authors.initials: NA
authors.lastname: Pelallo-Martínez
authors.affiliation: Toxicology Department, CINVESTAV-IPN, Mexico City, Mexico. Electronic address: maria.solis@cinvestav.mx.
authors.forename: María de Jesús
authors.initials: MJ
authors.lastname: Solís-Heredia
authors.affiliation: Harvard T.H. Chan School of Public Health, Boston MA, USA. Electronic address: Hyang-Min.Byun@newcastle.ac.uk.
authors.forename: Hyang-Min
authors.initials: HM
authors.lastname: Byun
authors.affiliation: Harvard T.H. Chan School of Public Health, Boston MA, USA. Electronic address: abaccare@hsph.harvard.edu.
authors.forename: Andrea
authors.initials: A
authors.lastname: Baccarelli
authors.affiliation: Toxicology Department, CINVESTAV-IPN, Mexico City, Mexico. Electronic address: mquintan@cinvestav.mx.
authors.forename: Betzabet
authors.initials: B
authors.lastname: Quintanilla-Vega
mesh_terms: D002648:Child; D003430:Cross-Sectional Studies; D004247:DNA / Q000378:metabolism*; D019175:DNA Methylation; D004260:DNA Repair / Q000235:genetics*; D004781:Environmental Exposure; D005260:Female; D006801:Humans; D008297:Male; D010084:Oxidation-Reduction; D012091:Repetitive Sequences, Nucleic Acid; D014505:Urban Population
chemical_list: D004247:DNA
keywords: Children’s health; DNA methylation; DNA repair; Genetic damage; PM exposure