In Vitro Toxicity and Epigenotoxicity of Different Types of Ambient Particulate Matter

被引:27
作者
Miousse, Isabelle R. [1 ]
Chalbot, Marie-Cecile G. [1 ]
Pathak, Rupak [2 ]
Lu, Xiaoyan [3 ]
Nzabarushimana, Etienne [1 ,4 ]
Krager, Kimberly [2 ]
Aykin-Burns, Nukhet [2 ]
Hauer-Jensen, Martin [2 ]
Demokritou, Philip [3 ]
Kavouras, Ilias G. [1 ]
Koturbash, Igor [1 ]
机构
[1] Univ Arkansas Med Sci, Fay W Boozman Coll Publ Hlth, Dept Environm & Occupat Hlth, Little Rock, AR 72205 USA
[2] Univ Arkansas Med Sci, Coll Pharm, Dept Pharmaceut Sci, Div Radiat Hlth, Little Rock, AR 72205 USA
[3] Harvard Univ, Sch Publ Hlth, Ctr Nanotechnol & Nanotoxicol, Dept Environm Hlth, Boston, MA 02115 USA
[4] Indiana Univ, Dept Biol, Bloomington, IN 47405 USA
基金
美国国家卫生研究院; 美国国家航空航天局;
关键词
chromosomal aberrations; DNA methylation; ambient particulate matter; satellite DNA; transposable elements; FINE ORGANIC AEROSOL; URBAN AIR COARSE; DNA METHYLATION; EPIGENETIC ALTERATIONS; CYTOTOXIC RESPONSES; SATELLITE REPEATS; TERM EXPOSURE; PARTICLES; HYPOMETHYLATION; POLLUTION;
D O I
10.1093/toxsci/kfv200
中图分类号
R99 [毒物学(毒理学)];
学科分类号
100405 ;
摘要
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 thein vitro system. RAW264.7 murine macrophages were exposed for 24 and 72 h to 5- and 50-mu g/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.
引用
收藏
页码:473 / 487
页数:15
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