title: Epigenetic alterations induced by ambient particulate matter in mouse macrophages.
abstract: Respiratory mortality and morbidity has been associated with exposure to particulate matter (PM). Experimental evidence suggests involvement of cytotoxicity, oxidative stress, and inflammation in the development of PM-associated pathological states; however, the exact mechanisms remain unclear. In the current study, we analyzed short-term epigenetic response to PM10 (particles with aerodynamic diameter less than 10 μm) exposure in mouse ascitic RAW264.7 macrophages (BALB/C Abelson murine leukemia virus-induced tumor). Ambient PM10 was collected using a high volume sampler in Little Rock, AR. Analysis revealed that PM10 was composed mainly of Al and Fe, and the water soluble organic fraction was dominated by aliphatic and carbohydrate fragments and minor quantities of aromatic components. Exposure to PM10 compromised the cellular epigenome at concentrations 10-200 µg/ml. Specifically, epigenetic alterations were evident as changes in the methylation and expression of repetitive element-associated DNA and associated DNA methylation machinery. These results suggest that epigenetic alterations, in concert with cytotoxicity, oxidative stress, and inflammation, might contribute to the pathogenesis of PM-associated respiratory diseases.
authors.affiliation: Department of Environmental and Occupational Health, College of Public Health, University of Arkansas for Medical Sciences, Little Rock, Arkansas.
authors.forename: Isabelle R
authors.initials: IR
authors.lastname: Miousse
authors.forename: Marie-Cécile G
authors.initials: MC
authors.lastname: Chalbot
authors.forename: Nükhet
authors.initials: N
authors.lastname: Aykin-Burns
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Wang
authors.forename: Alexei
authors.initials: A
authors.lastname: Basnakian
authors.forename: Ilias G
authors.initials: IG
authors.lastname: Kavouras
authors.forename: Igor
authors.initials: I
authors.lastname: Koturbash
mesh_terms: D044503:5-Methylcytosine / Q000032:analysis; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002478:Cells, Cultured; D019175:DNA Methylation / Q000187:drug effects*; D044127:Epigenesis, Genetic / Q000187:drug effects*; D020287:In Situ Nick-End Labeling; D007249:Inflammation / Q000139:chemically induced*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D018384:Oxidative Stress / Q000187:drug effects*; D052638:Particulate Matter / Q000633:toxicity*; D012091:Repetitive Sequences, Nucleic Acid / Q000187:drug effects*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D052638:Particulate Matter; D014409:Tumor Necrosis Factor-alpha; D044503:5-Methylcytosine; D007770:L-Lactate Dehydrogenase
keywords: DNA methylation; air pollution; repetitive elements