In Vitro Toxicity and Epigenotoxicity of Different Types of Ambient Particulate Matter.
Exposure to ambient particulate matter (PM) has been associated with adverse health effects, including pulmonary and cardiovascular disease. Studies indicate that ambient PM originated from different sources may cause distinct biological effects. In this study, we sought to investigate the potential of various types of PM to cause epigenetic alterations in the in vitro system. RAW264.7 murine macrophages were exposed for 24 and 72 h to 5- and 50-μg/ml doses of the water soluble extract of 6 types of PM: soil dust, road dust, agricultural dust, traffic exhausts, biomass burning, and pollen, collected in January-April of 2014 in the area of Little Rock, Arkansas. Cytotoxicity, oxidative potential, epigenetic endpoints, and chromosomal aberrations were addressed. Exposure to 6 types of PM resulted in induction of cytotoxicity and oxidative stress in a type-, time-, and dose-dependent manner. Epigenetic alterations were characterized by type-, time-, and dose-dependent decreases of DNA methylation/demethylation machinery, increased DNA methyltransferases enzymatic activity and protein levels, and transcriptional activation and subsequent silencing of transposable elements LINE-1, SINE B1/B2. The most pronounced changes were observed after exposure to soil dust that were also characterized by hypomethylation and reactivation of satellite DNA and structural chromosomal aberrations in the exposed cells. The results of our study indicate that the water-soluble fractions of the various types of PM have differential potential to target the cellular epigenome.
*Department of Environmental and Occupational Health, Fay W. Boozman College of Public Health and.
Isabelle R
IR
Miousse
*Department of Environmental and Occupational Health, Fay W. Boozman College of Public Health and.
Marie-Cecile G
MC
Chalbot
Division of Radiation Health, Department of Pharmaceutical Sciences, College of Pharmacy, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205;
Rupak
R
Pathak
Center for Nanotechnology and Nanotoxicology, Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts; and.
Xiaoyan
X
Lu
*Department of Environmental and Occupational Health, Fay W. Boozman College of Public Health and Department of Biology, Indiana University, Bloomington, Indiana 47405.
Etienne
E
Nzabarushimana
Division of Radiation Health, Department of Pharmaceutical Sciences, College of Pharmacy, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205;
Kimberly
K
Krager
Division of Radiation Health, Department of Pharmaceutical Sciences, College of Pharmacy, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205;
Nukhet
N
Aykin-Burns
Division of Radiation Health, Department of Pharmaceutical Sciences, College of Pharmacy, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205;
Martin
M
Hauer-Jensen
Center for Nanotechnology and Nanotoxicology, Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts; and.
Philip
P
Demokritou
*Department of Environmental and Occupational Health, Fay W. Boozman College of Public Health and.
Ilias G
IG
Kavouras
*Department of Environmental and Occupational Health, Fay W. Boozman College of Public Health and IKoturbash@uams.edu.
Igor
I
Koturbash
D000818:Animals; D002869:Chromosome Aberrations / Q000139:chemically induced*; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics / Q000378:metabolism; D019175:DNA Methylation / Q000187:drug effects*; D000090205:DNA Methyltransferase 3A; D004251:DNA Transposable Elements; D004276:DNA, Satellite; D004305:Dose-Response Relationship, Drug; D044127:Epigenesis, Genetic / Q000187:drug effects*; D057890:Epigenomics / Q000379:methods; D015971:Gene Expression Regulation, Enzymologic; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D052638:Particulate Matter / Q000633:toxicity*; D000067996:RAW 264.7 Cells; D013997:Time Factors; D000097584:DNA Methyltransferase 3B
D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; D000090205:DNA Methyltransferase 3A; D004251:DNA Transposable Elements; D004276:DNA, Satellite; D052638:Particulate Matter; D000097584:DNA Methyltransferase 3B
DNA methylation; ambient particulate matter; chromosomal aberrations; satellite DNA; transposable elements