Toxicological study at inflammatory factors and DNA damages effects of Beijing atmospheric PM2.5 and its different fractions to pulmonary epithelial cells A549 of human
JIAO Zhou-guang1, FU Xu-lei2, WEN Zhan-bo1, LI Jin-song1, LI Na1, ZHANG Ke1, WANG Jie1, HU Ling-fei1
1. State Key Laboratory of Pathogen and Biosecurity, Institute of Microbiology and Epidemiology, Academy of Military Medical Sciences, Beijing 100071, China;
2. College of Food Science and Technology, Bohai University, Jinzhou 121013, China
In order to investigate the toxicity effect of atmospheric PM2.5 and its different fractions to human pulmonary epithelial cells A549 with respect to the relationship between PM2.5 dosage and cell response, the water-soluble, fat-soluble, pure particle fractions of PM2.5 (designated WSP2.5, FSP2.5 and PPP2.5, respectively) prepared from original PM2.5 samples (designated OP2.5) and OP2.5 were to treat A549 cells at different PM concentrations (10, 50, 100, 200, 400μg/mL, respectively). The MTS method was used to test the cell viability at 6h, 10h, 24h, 48h and 72h post-treatment, while ELISA and RT-QPCR were employed to detect the production of inflammatory cytokines IL-6 and TNF-α and the AP-sites counting was conducted to determine the level of intracellular DNA damage at 24h post-treatment. WSP2.5 had very limited effect to inhibit cell growth and induce inflammatory damages and DNA base deletion. FSP2.5, PPP2.5 and OP2.5 at high concentrations showed the inhibitory effect to cell growth across treatment; when cells were treated with low concentrations of FSP2.5, PPP2.5 or OP2.5, the inhibition of cell growth occurred within a short period and then disappeared over time. FSP2.5, PPP2.5 andOP2.5 treatment significantly induced the production of IL-6at both mRNA and protein levels, while WSP2.5, PPP2.5 andOP2.5 treatment significantly induced the mRNA expression of TNF-α. FSP2.5, PPP2.5 and OP2.5 treatment also induced the considerable DNA base deletion. In a word, not only the complex components adsorbed on the solid core granules of PM2.5, but also the solid core granules themselves contributed to the cytotoxicity effects.
焦周光, 付绪磊, 温占波, 李劲松, 李娜, 张柯, 王洁, 胡凌飞. 北京大气PM2.5对A549细胞炎性因子及DNA损伤的毒性[J]. 中国环境科学, 2016, 36(5): 1579-1588.
JIAO Zhou-guang, FU Xu-lei, WEN Zhan-bo, LI Jin-song, LI Na, ZHANG Ke, WANG Jie, HU Ling-fei. Toxicological study at inflammatory factors and DNA damages effects of Beijing atmospheric PM2.5 and its different fractions to pulmonary epithelial cells A549 of human. CHINA ENVIRONMENTAL SCIENCECE, 2016, 36(5): 1579-1588.
Nemmar A, Hoet PH, Vanquickenborne B, et al. Passage of inhaled particles into the blood circulation in humans [J]. Circulation, 2002,105(4):411-414.
[2]
Oberdorster G. Pulmonary effects of inhaled ultrafine particles [J]. International Archives of Occupational and Environmental Health, 2001,74(1):1-8.
[3]
Donaldson K, Stone V, Seaton A, et al. Ambient particle inhalation and the cardiovascular system: potential mechanisms [J]. Environmental Health PerspectIves, 2001,109Suppl 4:523-527.
[4]
Lim SS, Vos T, Flaxman AD, et al. A comparative risk assessment of burden of disease and injury attributable to 67risk factors and risk factor clusters in 21regions, 1990~2010: a systematic analysis for the Global Burden of Disease Study 2010 [J]. Lancet, 2012,380(9859):2224-2260.
[5]
Peng R D, Bell M L, Geyh A S, et al. Emergency admissions for cardiovascular and respiratory diseases and the chemical composition of fine particle air pollution [J]. Environmental Health PerspectIves, 2009,117(6):957-963.
[6]
Pope Ⅲ CA, Burnett RT, Thun MJ, et al. Lung cancer, cardiopulmonary mortality, and long-term exposure to fine particulate air pollution [J]. Jama, 2002,287(9):1132-1141.
Ulrich M M, Alink G M, Kumarathasan P, et al. Health effects and time course of particulate matter on the cardiopulmonary system in rats with lung inflammation [J]. Journal of Toxicology and Environmental Health Part A, 2002,65(20):1571-1595.
[9]
Muller B, Seifart C, Barth PJ. Effect of air pollutants on the pulmonary surfactant system [J]. European Journal of Clinical Investigation, 1998,28(9):762-777.
[10]
Xu H, Wang X, Poschl U, et al. Genotoxicity of total and fractionated extractable organic matter in fine air particulate matter from urban Guangzhou: comparison between haze and nonhaze episodes [J]. Environmental Toxicology and Chemistry/ SETAC, 2008,27(1):206-212.
[11]
Hiura T S, Kaszubowski M P, Li N, et al. Chemicals in diesel exhaust particles generate reactive oxygen radicals and induce apoptosis in macrophages [J]. Journal of Immunology, 1999, 163(10):5582-5591.
[12]
Ghio A J, Stonehuerner J, Dailey L A, et al. Metals associated with both the water-soluble and insoluble fractions of an ambient air pollution particle catalyze an oxidative stress [J]. Inhalation Toxicology, 1999,11(1):37-49.
[13]
Prahalad A K, Soukup J M, Inmon J, et al. Ambient air particles: effects on cellular oxidant radical generation in relation to particulate elemental chemistry [J]. Toxicology and Applied Pharmacology, 1999,158(2):81-91.
[14]
Rumelhard M, Ramgolam K, Auger F, et al. Effects of PM2.5components in the release of amphiregulin by human airway epithelial cells [J]. Toxicology Letters, 2007,168(2):155-164.
Pozzi R, De Berardis B, Paoletti L, et al. Inflammatory mediators induced by coarse (PM2.5-10) and fine (PM2.5) urban air particles in RAW 264.7cells [J]. Toxicology, 2003,183(1-3):243-254.
Ding X, Wang M, Chu H, et al. Global gene expression profiling of human bronchial epithelial cells exposed to airborne fine particulate matter collected from Wuhan, China [J]. Toxicology Letters, 2014,228(1):25-33.
Obot C J, Morandi M T, Beebe T P, et al. Surface components of airborne particulate matter induce macrophage apoptosis through scavenger receptors [J]. Toxicology and Applied Pharmacology, 2002,184(2):98-106.
Vanhee D, Gosset P, Marquette C H, et al. Secretion and mRNA expression of TNF alpha and IL-6in the lungs of pneumoconiosis patients [J]. American Journal of Respiratory and Critical Care Medicine, 1995,152(1):298-306.
[30]
Ulich T R, Yin S, Guo K, et al. Intratracheal injection of endotoxin and cytokines. II. Interleukin-6and transforming growth factor beta inhibit acute inflammation [J]. The American Journal of Pathology, 1991,138(5):1097-1101.
Risom L, Moller P, Loft S. Oxidative stress-induced DNA damage by particulate air pollution [J]. Mutation Research, 2005, 592(1/2):119-137.
[36]
Shi T, Duffin R, Borm PJ, et al. Hydroxyl-radical-dependent DNA damage by ambient particulate matter from contrasting sampling locations [J]. Environmental Research, 2006,101(1): 18-24.
[37]
Valko M, Izakovic M, Mazur M, et al. Role of oxygen radicals in DNA damage and cancer incidence [J]. Molecular and Cellular Biochemistry, 2004,266(1/2):37-56.
[38]
Rossi O, Carrozzino F, Cappelli E, et al. Analysis of repair of abasic sites in early onset breast cancer patients [J]. International Journal of Cancer, 2000,85(1):21-26.
[39]
Sun H B, Qian L, Yokota H. Detection of abasic sites on individual DNA molecules using atomic force microscopy [J]. Analytical Chemistry, 2001,73(10):2229-2232.
